Systems, devices, and methods for fluid monitoring

ABSTRACT

Devices, systems, and methods herein relate to predicting infection of a patient. These systems and methods may comprise illuminating a patient fluid in a fluid conduit from a plurality of illumination directions, measuring an optical characteristic of the illuminated patient fluid using one or more sensors, and predicting an infection state of the patient based at least in part on the measured optical characteristic.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 62/867,157, filed on Jun. 26, 2019, the content of which is herebyincorporated by reference in its entirety.

FIELD

Devices, systems, and methods herein relate to fluid monitoring that maybe used in diagnostic and/or therapeutic applications, including but notlimited to infection prediction.

BACKGROUND

Several chronic diseases rely on patient self-administration or homecaretaker administration of treatment in outpatient settings, includinginfusion into and/or drainage of fluids from the body via catheters ortubes. Some patients visit dialysis clinics on a weekly or monthly basisto perform a visual inspection for infections, to review patient data(e.g., manual records, night cycler data) for patient compliance, and tomonitor treatment efficacy via blood draws. However, patients typicallyself-diagnose based on apparent signs of infection and are relied uponto timely report possible complications to a health care professional.Therefore, additional devices, systems, and methods for monitoringpatient complications such as infection origination may be desirable.

SUMMARY

Described here are patient monitoring systems and devices and methodsfor detecting infection of a patient. These systems and methods may, forexample, monitor patient fluid and analyze characteristics of thepatient fluid to generate patient data that may be used to predict aninfection state that may be presented to the patient and/or health careprofessional. This may, for example, allow the health care professionalto prescribe a treatment plan at the onset of infection in order toquickly resolve the infection and reduce the need for costlyhospitalization. Furthermore, the patient's response to treatment (e.g.,an antibiotic regimen) may be monitored remotely over time and allow thetreatment plan to be updated in real-time. The systems and devicesdescribed here are configured to retrofit a variety of existing dialysiscatheters and dialysate infusion systems, including continuous cyclingperitoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis(CAPD) systems.

Generally, methods of predicting infection of a patient may include thesteps of illuminating a patient fluid in a fluid conduit from aplurality of illumination directions. An optical characteristic of theilluminated patient fluid may be measured using one or more sensors. Aninfection state of the patient may be predicted based at least in parton the measured optical characteristic.

In some variations, the plurality of illumination directions maycomprise a first illumination direction and a second illuminationdirection orthogonal to the first illumination direction. In some ofthese variations, the predicted infection state of the patient may bebased at least in part on one or more 90-degree scatter angle lightintensity measurements from the one or more sensors. In some of thesevariations, the predicted infection state of the patient may further bebased at least in part on one or more 180-degree attenuation lightintensity measurements from the one or more sensors.

In some variations, the plurality of illumination directions maycomprise a first illumination direction and a second illuminationdirection 180 degrees offset from the first illumination direction.

In some variations, illuminating the patient fluid may compriseilluminating the patient fluid at a first wavelength from a firstillumination direction and at the first wavelength from a secondillumination direction. The first and second illumination directions mayextend along a first plane. In some variations, illuminating the patientfluid may comprise illuminating the patient fluid along at least thefirst plane and along a second plane substantially parallel to the firstplane.

In some variations, the plurality of wavelengths may comprise a firstwavelength between about 800 nm and about 900 nm. In some of thesevariations, illuminating the patient fluid may comprise illuminating thepatient fluid sequentially at a plurality of wavelengths including thefirst wavelength. In some of these variations, the plurality ofwavelengths may comprise a second wavelength between about 400 nm andabout 450 nm, and a third wavelength between about 500 nm and about 550nm. In some of these variations, illuminating the patient fluid maycomprise sequentially illuminating the patient fluid at the thirdwavelength, the first wavelength, and then the second wavelength. Insome of these variations, the plurality of wavelengths may comprise afourth wavelength between about 230 nm and about 290 nm.

In some variations, the optical characteristic may comprise one or moreof optical scatter and attenuation detection angle. In some variations,predicting the infection state may comprise generating an infectionscore and/or an infection probability. In some of these variations,estimating turbidity of the patient fluid may be based at least in parton the measured optical characteristic. The infection score may be basedat least in part on the estimated turbidity. In some of thesevariations, predicting the infection state may comprise predictinginfection in response to the infection score exceeding a predeterminedthreshold during each of one or more successive measurement timeperiods. In some of these variations, predicting the infection state maycomprise predicting infection in response to the infection scoreincreasing from a patient baseline over time. In some of thesevariations, predicting the infection state may comprise predictinginfection based on a rate of change of the infection score over time.

In some variations, predicting the infection state may comprisepredicting infection in response to any one or more of the following:the infection score exceeding a predetermined threshold during each ofone or more successive measurement time periods, the infection scoreincreasing from a patient baseline over time, and the infection scorehaving an increasing rate of change over time. In some variations,predicting the infection state may comprise predicting a probability ofinfection.

In some variations, the fluid conduit may be coupled to a peritonealdialysis device fluid path. In some variations, the fluid conduit may becoupled to a peritoneal dialysis device tubing set. In some variations,the fluid conduit may be coupled to an inlet of the peritoneal dialysisdevice tubing set. In some variations, the fluid conduit may be coupledto an outlet of the peritoneal dialysis device tubing set. In somevariations, the fluid conduit may be coupled to a drain line of aperitoneal dialysis cycler tubing set. In some variations, the fluidconduit may be coupled to a drain line extension configured to couple toa peritoneal dialysis cycler tubing set drain line. In some variations,the fluid conduit may be coupled to a patient line of a peritonealdialysis cycler tubing set. In some variations, the fluid conduit may becoupled to a peritoneal dialysis device tubing set.

In some variations, a fluid flow rate in the fluid conduit may beestimated based at least in part on the measured optical characteristic.Illuminating the patient fluid may comprise activating illuminationbased on the estimated fluid flow rate. In some of these variations,determining a fluid flow state may comprise detecting at least one of anON state and an OFF state based on the estimated fluid flow rate.Illuminating the patient fluid may comprise activating illumination inresponse to detecting the ON state and ceasing illumination in responseto detecting the OFF state.

In some variations, identifying a false positive fluid flow state may bebased on the estimated fluid flow rate. In some variations, identifyingthe false positive fluid flow state may comprise detecting apredetermined number of pulses during less than each of one or moresuccessive measurement time periods. In some variations, detecting theON state may comprise detecting a predetermined number of pulses duringeach of one or more successive measurement time periods. In somevariations, one or more successive measurement time periods may beseparated by a predetermined delay time period. In some variations,estimating the fluid flow rate may be based at least in part on applyingone or more of a low pass filter and a high pass filter to the measuredoptical characteristic. In some variations, initiating illuminating thepatient fluid and measuring the optical characteristic may be based on auser input.

In some variations, detecting a bubble in the fluid conduit may be basedat least in part on the optical measurement. In some variations, anindication of the predicted infection state may be provided to a user.In some variations, a particle concentration of the patient fluid may bepredicted based at least in part on the measured optical characteristic.In some variations, bleeding of the patient may be predicted based atleast in part on the measured optical characteristic. In somevariations, an immune response of the patient may be predicted based atleast in part on the measured optical characteristic. In somevariations, predicting infection onset may be predicted for ascitesdrainage patients based at least in part on the measured opticalcharacteristic. In some variations, a fibrin content of the patientfluid may be predicted based at least in part on the measured opticalcharacteristic.

Also described here are vessels for use in a fluid conduit. The vesselmay comprise an inlet portion, an outlet portion, and a generallyoptically transparent measurement portion between the inlet portion andthe outlet portion. The measurement portion may comprise at least twosubstantially planar surfaces and a depth alignment feature.

In some variations, the measurement portion may comprise an internalvolume configured to receive fluid. The internal volume may compriseradiused corners. In some of these variations, the at least twosubstantially planar surfaces may comprise a first planar surfacegenerally orthogonal to a second planar surface. In some of thesevariations, the at least two substantially planar surfaces may comprisea first planar surface opposite to a second planar surface. In some ofthese variations, the measurement portion may comprise a generallysquare cross-section.

In some variations, at least a portion of the measurement portion may betapered. In some variations, the measurement portion may comprise one ormore of copolyester, acrylonitrile butadiene styrene, polycarbonate,acrylic, cyclic olefin copolymer, cyclic olefin polymer, polyester,polystyrene, ultem, polyethylene glycol-coated silicone, zwitterioniccoated polyurethane, polyethylene oxide-coated polyvinyl chloride, andpolyamphiphilic silicone.

In some variations, an opaque connector may be coupleable to the inletportion or the outlet portion. In some of these variations, at least oneof the inlet portion and the outlet portion may be coupleable to thefluid conduit. In some of these variations, one or more of a vent cap,clamp, and connector may be coupled to the fluid conduit. In somevariations, the vessel may be coupled to a peritoneal dialysis drain setextension tubing.

In some variations, the vessel may be coupled to a peritoneal dialysiscycler tubing cassette. In some variations, the vessel may be coupled toan inlet of a peritoneal dialysis cycler tubing cassette. In somevariations, the vessel may be coupled to a peritoneal dialysis drain bagconnector. In some variations, the vessel may be coupled to a proximalend of a peritoneal dialysis drain bag connector. In some variations,the vessel may be coupled to a urinary catheter or Foley catheter drainbag. In some variations, the vessel may be coupled to a central venousdrain line. In some variations, the vessel may be coupled to ahemodialysis blood circulation tube set. In some variations, the vesselmay be coupled to an in-dwelling catheter. In some variations, thevessel may be coupled to a proximal end of the in-dwelling catheter

Also described here are patient monitoring devices comprising a housing.The housing may comprise a holder configured to releasably receive aportion of a fluid conduit. At least one illumination source may beconfigured to illuminate the received portion of the fluid conduit. Atleast one optical sensor may be configured to generate a signal. Theholder may comprise an engagement feature configured to orient thereceive portion of the fluid conduit in a predetermined rotational andvertical orientation relative to the at least one illumination sourceand the at least one optical sensor.

In some variations, the housing may comprise a light seal. In somevariations, the one or more engagement features may be configured toorient the received portion of the fluid conduit by mating with analignment feature of the received portion of the fluid conduit. In somevariations, the one or more engagement features may comprise an openslot.

In some variations, the at least one illumination source may comprises aplurality of illumination sources. In some of these variations, theillumination sources may be configured to illuminate in a firstillumination direction and a second illumination direction orthogonal tothe first illumination direction.

In some variations, at least two of the illumination sources may beconfigured to illuminate along a first plane at a first wavelength. Insome variations, at least another two of the illumination sources may beconfigured to illuminate along a second plane substantially parallel tothe first plane. In some variations, the illumination sources may beconfigured to illuminate in a first illumination direction and a secondillumination direction opposite the first direction.

In some of these variations, the illumination sources may be configuredto illuminate in a first illumination direction and a secondillumination direction 180 degrees offset from the first direction. Insome of these variations, the illumination sources may comprise a firstillumination source configured to emit light at a first wavelengthbetween about 800 nm and about 900 nm. In some of these variations, theillumination sources may comprise a second illumination sourceconfigured to emit light at a second wavelength between about 400 nm andabout 450 nm. In some of these variations, the illumination sources maycomprise a third illumination source configured to emit light at a thirdwavelength between about 500 nm and about 550 nm. In some of thesevariations, the illumination sources may comprise a fourth illuminationsource configured to emit light at a third wavelength between about 230nm and about 290 nm.

In some variations, the at least one optical sensor may comprise aplurality of optical sensors. In some variations, one or more of the atleast one illumination source and the at least one optical sensor maycomprise an anti-reflective coating. In some of these variations, theholder may define a longitudinal axis, and the optical sensors may bespaced apart parallel to the longitudinal axis.

In some variations, a controller may be configured to generate patientdata based at least in part on the signal. In some variations, thepatient data may comprise an infection state. In some variations, thedevice may further comprise a display. In some variations, the devicemay further comprise a communication device. In some variations, thedevice may comprise a base. The housing may be offset and spaced apartfrom the base. In some variations, the housing may comprise a peritonealdialysis cycler. In some variations, the housing may comprise ahemodialysis device. In some variations, the housing may be configuredto couple to one or more of a patient platform and medical cart.

In some variations, the housing may comprise a peritoneal dialysisdevice fluid path. In some variations, the fluid conduit may be coupledto a peritoneal dialysis tubing set. In some variations, the fluidconduit may be coupled to a peritoneal dialysis cycler tubing set. Insome variations, the fluid conduit may be coupled to a peritonealdialysis drain bag connector. In some variations, the fluid conduit maycomprise an inlet portion, an outlet portion, and an opticallytransparent measurement portion between the inlet portion and the outletportion, wherein the measurement portion comprises at least twosubstantially planar surfaces, a rotational alignment feature, and adepth alignment feature.

In some variations, at least one of the rotational alignment feature andthe depth alignment feature may be configured to mate with the one ormore engagement features of the holder. In some variations, a controllermay be configured to generate patient data based at least in part on thesignal. In some variations, the controller may be located remote fromthe housing. The device may further comprise a communication deviceconfigured to transmit data representative of the signal to thecontroller. In some variations, the controller may be configured topredict an infection score of a patient based at least in part on thesignal. In some variations, the controller may be configured to predictan infection state of a patient in response to any one or more of thefollowing: the infection score exceeding a predetermined thresholdduring each of one or more successive measurement time periods, theinfection score increasing from a patient baseline over time, and theinfection score having an increasing rate of change over time. In somevariations, the infection state may comprise a probability of infection.In some variations, the fluid conduit may be configured to receive apatient fluid and the controller may be configured to estimate turbidityof the patient fluid based at least in part on the signal, wherein theinfection score is based at least in part on the estimated turbidity.

In some variations, the controller may be configured to monitor a trendin infection score predicting infection resolution of the patient. Insome variations, the controller may be configured to monitor a trend ininfection score predicting infection resolution of the patient bypredicting infection resolution in response to any one or more of thefollowing: the infection score falling below a predetermined thresholdduring each of one or more successive measurement time periods, theinfection score decreasing from a patient baseline over time, and theinfection score having a decreasing rate of change over time.

Also described are methods for remote monitoring of a patient, that mayinclude the steps of, at one or more processors, receiving an opticalcharacteristic measurement of a patient fluid associated with thepatient over a remote communication link. An infection score may bedetermined for predicting infection of the patient. The infection scoremay be based at least in part on the received optical characteristicmeasurement. In some variations, the patient may be associated with oneof a plurality of patient infection states based at least in part on thedetermined infection score. In some variations, a user may be notifiedof the associated patient infection state.

In some variations, a user may be prompted to perform one or morepredetermined patient treatment actions based on the associated patientinfection state. In some of these variations, the one or morepredetermined patient treatment actions may comprise administering abroad spectrum antimicrobial to the patient. In some of thesevariations, the one or more predetermined patient treatment actions maycomprise administering a pathogen-specific antimicrobial (e.g.,antibiotic, antifungal, antiviral) to the patient. In some of thesevariations, the one or more predetermined patient treatment actions maycomprise remotely monitoring a trend in infection score predictinginfection resolution of the patient (based on the resultant efficacy ofthe antimicrobial treatment).

In some variations, remotely monitoring the trend in infection scorepredicting infection resolution may comprise predicting infectionresolution in response to the infection score decreasing from a patientbaseline over time. In some variations, remotely monitoring the trend ininfection score predicting infection resolution comprises predictinginfection resolution based on a rate of change of the infection scoreover time. In some variations, remotely monitoring the trend ininfection score predicting infection resolution comprises predictinginfection resolution in response to any one or more of the following:the infection score falling below a predetermined threshold during eachof one or more successive measurement time periods, the infection scoredecreasing from a patient baseline over time, and the infection scorehaving a decreasing rate of change over time.

In some variations, the plurality of patient infection states maycomprise a first patient infection state corresponding to a healthypatient. In some variations, the plurality of patient infection statesmay comprise a second patient infection state corresponding to a patientbrought to a medical care provider. In some variations, the plurality ofpatient infection states may comprise a third patient infection statecorresponding to a patient who has received a broad spectrumantimicrobial treatment. In some variations, the plurality of patientinfection states may comprises a third patient infection statecorresponding to a patient who has received a pathogen-specificantimicrobial treatment. In some variations, the plurality of patientinfection states may comprise a fourth patient infection statecorresponding to a patient who has been hospitalized. In somevariations, the plurality of patient infection states may comprise afifth patient infection state corresponding to a patient who has beentransitioned to hemodialysis. In some variations, the predictedinfection may be peritonitis.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a block diagram of an illustrative variation of a patientmonitoring system.

FIG. 2 depicts a schematic diagram of an illustrative variation of apatient monitoring system.

FIGS. 3A and 3B depict right and left perspective views, respectively,of an illustrative variation of a patient monitoring device.

FIGS. 4A, 4B, and 4C depict block diagrams of other illustrativevariations of a patient monitoring system.

FIGS. 5A, 5B, 5C, and 5D depict schematic diagrams of other illustrativevariations of a patient monitoring system.

FIG. 6 depicts a block diagram of an illustrative variation of a patientmonitoring device.

FIG. 7A depicts a perspective view of an illustrative variation of apatient monitoring device. FIG. 7B depicts an exploded schematic diagramof the patient monitoring device shown in FIG. 7A. FIG. 7C depicts aperspective view of an illustrative variation of a patient monitoringdevice coupled to a vessel and in an open configuration. FIG. 7D depictsa perspective view of an illustrative variation of a patient monitoringdevice also in the open configuration. The patient monitoring device iscoupled to a vessel attached to a fluid conduit.

FIGS. 8A and 8D depict perspective views of an illustrative variation ofa patient monitoring device in a closed configuration. FIG. 8B depicts aperspective view of an illustrative variation of a patient monitoringdevice in an open configuration. FIG. 8C depicts a side view of anillustrative variation of a patient monitoring device in an openconfiguration.

FIG. 9A depicts a perspective view of an illustrative variation of apatient monitoring device in an open configuration. FIG. 9B depicts aperspective view of an illustrative variation of a fluid conduit and apatient monitoring device in an open configuration. FIG. 9C depicts aperspective view

FIG. 10A is an exploded perspective view of an illustrative variation ofa holder of a patient monitoring device. FIG. 10B is an explodedperspective view of an illustrative variation of an optical sensorarrangement of a patient monitoring device. FIG. 10C is across-sectional schematic view of an illustrative variation of anoptical sensor arrangement of a patient monitoring device. FIG. 10D is aplan view of an illustrative variation of a holder of a patientmonitoring device. FIG. 10E is a perspective view of an illustrativevariation of a holder of a patient monitoring device. FIG. 1OF is anexploded perspective view of an illustrative variation of an opticalsensor arrangement of a patient monitoring device.

FIG. 11A is a side view of an illustrative variation of an opticalsensor arrangement of a patient monitoring device. FIG. 11B is across-sectional view of the optical sensor arrangement depicted in FIG.11A, taken along line A:A.

FIGS. 12A and 12B are schematic perspective views of an illustrativevariation of a vessel and an optical sensor arrangement of a patientmonitoring device.

FIG. 13 is a schematic diagram of an illustrative variation of anoptical sensor arrangement of a patient monitoring device.

FIGS. 14A and 14B are schematic diagrams of illustrative variations ofan optical sensor arrangement.

FIG. 15 depicts illustrative variations of a graphical user interface ofa patient monitoring device.

FIG. 16A is a perspective view of an illustrative variation of a drainline extension. FIG. 16B is an exploded perspective view of the drainline extension depicted in FIG. 16A.

FIG. 17A is a perspective view of another illustrative variation of adrain line extension. FIG. 17B is an exploded perspective view of thedrain line extension depicted in FIG. 17A. FIG. 17C is a perspectiveview of another illustrative variation of a drain line.

FIGS. 18A, 18B, and 18F are cross-sectional side views of anillustrative variation of a vessel. FIGS. 18C, 18D, 18E, and 18H areperspective views of an illustrative variation of a vessel. FIG. 18G isa bottom plan view of an illustrative variation of a vessel. FIG. 181 isa detail view of section area B of FIG. 18H.

FIGS. 19A and 19B are perspective views of an illustrative variation ofa cap. FIG. 19C is a cross-sectional side view of an illustrativevariation of a cap. FIG. 19D is a cross-sectional perspective view ofthe cap depicted in FIG. 19C.

FIG. 20 is an illustrative graph of estimated turbidity plotted overtime.

FIG. 21A depicts illustrative infection detection graphs of infectionscore plotted over time. FIG. 21B is an illustrative infection detectiongraph of cell concentration and infection score plotted over time.

FIGS. 22A and 22B are illustrative fluid flow graphs of optical sensormeasurements plotted over time and a corresponding frequency responseplot.

FIGS. 23A, 23B, 23C, and 23D are illustrative error measurement graphsfor respective leukocytes, erythrocytes, proteins, and triglycerides.

FIG. 24 is an illustrative graph of optical sensor measurements plottedover time for depiction of bubbles.

FIG. 25A is a schematic side view diagram of an illustrative variationof a cassette for use with a peritoneal dialysis cycler with an opticalmeasurement region. FIG. 25B is a schematic top view diagram of anillustrative variation of a cassette with an optical measurement regioninterface for an optical sensor(s) of a peritoneal dialysis cycler.

FIG. 26 is an exploded perspective view of an illustrative variation ofa vessel disposed in a holder of a patient monitoring device.

FIG. 27A is a schematic diagram of an illustrative clinical workflow inconvention standard of care. FIG. 27B is a schematic diagram of anillustrative clinical workflow using systems and methods describedherein.

FIG. 28 is a schematic diagram of a system for patient monitoringincluding one or more patient monitoring devices such as that describedherein.

FIG. 29 is a schematic diagram of patient stages in an illustrativevariation of a patient state diagram.

FIGS. 30-35 are exemplary graphical user interfaces (GUIs) for use in asystem for patient monitoring.

DETAILED DESCRIPTION

Described herein are methods, systems, and devices for monitoringpatient fluid. The methods described herein may predict infection of apatient. In some variations, the systems and devices may monitorpatients with end-stage renal disease that are prescribed peritonealdialysis. For example, the systems described herein may comprise apatient monitoring device and a fluid conduit (e.g., disposable drainline extension) coupled between drain line tubing of a peritonealdialysis night cycler and a drainage vessel such as a toilet. In somevariations, the fluid conduit may comprise a vessel configured to bereleasably received within a housing of the patient monitoring device.The fluid conduit may be independent of or integrated with another fluidconduit (e.g., drain line of a tubing set, other drain line extension,in-dwelling catheter, cassette). The patient monitoring device maycomprise an optical sensor configured to measure the patient fluidthrough the vessel and generate a signal corresponding to one or morecharacteristics of a patient fluid flowing through the vessel. Forexample, the measured characteristic may be used to predict an infectionstate of the patient (e.g., probability of infection), estimate particleconcentrations of the patient fluid, determine an operation state of acycler (e.g., flow ON, flow OFF), fluid flow through the fluid conduit,and/or detect noise components (e.g., bubbles) of the patient fluid.

These systems and devices may be used in an ambulatory or home-basedsetting for continuous monitoring of complications, including but notlimited to infections, catheter leakages, and catheter blockages.Patient compliance with the prescribed treatment may be monitored andcommunicated to the patient and/or health care providers. Treatmentefficacy may also be remotely monitored over time to indicate apatient's response to the prescribed treatment. As such, providers maymonitor patients more frequently than what may be practical throughsolely in-person clinic visits. Infections may be predicted andquantified in real-time and allow providers to address complicationsbefore problems exacerbate and become more difficult to resolve. Forexample, when detected and treated early, infections may be treated withan antibiotic regimen that may prevent patient hospitalization.Infection resolution may be monitored upon initiation of the antibiotictreatment and may be updated at predetermined intervals. For example,when treatment efficacy is positive, the prescribed medical therapy(e.g., drug, dosage, frequency) may be updated immediately to limit theantibiotics taken by the patient to the minimum necessary to resolve theinfection. In some variations, the systems, devices, and methodsdisclosed herein may comprise one or more systems, devices, and methodsof treatment administration and sample collection described inInternational Patent Application Serial No. PCT/US2018/065853, filed onDec. 14, 2018, the contents of which are hereby incorporated byreference in its entirety. For example, the tool may automateantimicrobial administration and/or culture sample collection (e.g.,based on algorithmic determination of infection score as describedbelow), which may reduce response periods from patient and/or medicalcare provider(s), thereby improving patient outcomes.

In some variations, a patient monitoring system may comprise a sensorconfigured to monitor fluid flowing from a peritoneal dialysis machine(“cycler”) to a drainage vessel. FIG. 1 depicts a block diagram of apatient monitoring system (100) comprising a cycler, drain line (120),sensor (130), fluid conduit (140), and drainage vessel (150). In somevariations, the cycler (110) may be configured to pump patient fluid(e.g., dialysate) into the drain line (120). The drain line (120) may befluidly coupled to the fluid conduit (140) and a drainage vessel (150)(e.g., toilet, drain pan, drain basin, waste bucket, waste bag, tub,sink, etc.) may be configured to receive the patient fluid. A portion ofthe fluid conduit (140) may be received by and aligned to the sensor(130) to measure an optical characteristic of the patient fluid throughthe fluid conduit (140), as described in more detail herein.

FIG. 2 depicts a schematic diagram of a patient monitoring system (200)that may be used in, for example, a patient's home or in a clinicsetting. The patient monitoring system (200) may comprise a cycler(210), drain line (220), patient monitoring device (230), fluid conduit(240), and drainage vessel (250, 260). In some variations, the cycler(210) may be configured to pump patient fluid (e.g., dialysate) into thedrain line (220). The drain line (220) may be fluidly coupled to thefluid conduit (240) and a drainage vessel such as toilet (250) or bag(260) may be configured to receive the patient fluid. A portion of thefluid conduit (140) may be received by and aligned to the patientmonitoring device (230). For example, the patient monitoring device(230) may comprise an optical sensor configured to measure an opticalcharacteristic of the patient fluid through the fluid conduit (240). Insome variations, an optically transparent vessel may be received andaligned to the patient monitoring device (230). The patient monitoringdevice (230) may be a durable component comprising a sensor configuredto measure and analyze the patient fluid in a non-contact manner, andnotify one or more of the patient and provider of the analysis. At leastin part because the fluid conduit (240) and patient monitoring device(230) retrofit into conventional dialysis setups, the use of the fluidconduit (240) and patient monitoring device (230) with a cycler (210)system may add only a relatively small amount of time and number ofsteps to a patient's dialysis setup and maintenance routine whileproviding real-time patient monitoring of patient fluid for infectiondetection and fluid characteristics.

In some variations, the fluid conduit and/or vessel may be a disposablecomponent that may be replaced at predetermined intervals (e.g., after adialysis session, daily, weekly, etc.). The fluid conduit and/or vesselmay serve as a drain line extension of a predetermined length and maycomprise one or more connectors configured to fluidly couple toconventional tubing connectors. For example, the fluid conduit mayextend a drain line to a predetermined length so as to provide fluidicconnection between a cycler (210) placed in a bedroom and a toilet (250)or other drainage vessel placed in a bathroom. In some variations, thepatient monitoring device (230) may be configured to attach to one ormore of a patient platform, a medical cart, and medical device (e.g., IVpole). A patient platform may include, for example, a surface for apatient (bed, chair, table, hospital bed, intensive care unit bed,etc.).

Also described are methods that may be performed using the systems anddevices described herein. In some variations, methods of predictinginfection of a patient may predict an infection state of the patientbased on an estimated turbidity of the patient fluid. For example,generally, infection may be correlated with the concentration of one ormore particle types, such as leukocytes, in the patient fluid. Theconcentration of leukocytes and/or other particle types may be estimatedbased on various optical parameters (e.g., turbidity) of the patientfluid, as estimated using methods and devices such as those describedherein. The estimated turbidity may be estimated based on a measuredoptical characteristic of the patient fluid. For example, the opticalcharacteristic may comprise one or more of optical scatter andobscuration light intensity measurements.

In some variations, the composition of a patient fluid may be estimatedbased on measured optical characteristics of a patient fluid. Inparticular, the type and concentration of particles in the patient fluidmay be estimated based on optical measurements. The particles maycomprise, for example, leukocytes, erythrocytes, protein, andtriglycerides. For example, the optical characteristics may be measuredat a plurality of wavelengths. In another example, the composition maybe estimated based on an optical characteristic of static patient fluidmeasured over a predetermined time period.

In some variations, an infection score of the patient may be predictedbased on a set of measured optical characteristics generated over time.For example, the infection score may be compared to a predeterminedthreshold or patient baseline to predict the state of infection such asonset and resolution. Analyzing a set of infection scores over time (asa surrogate for the rate of change of measured optical characteristics)may reduce false positives and thereby improve the sensitivity andspecificity of patient diagnosis and allow prediction of a patientinfection state (e.g., probability of infection).

In some variations, a patient infection state may comprise a firstinfection state corresponding to an infected patient and a secondinfection state corresponding to an uninfected patient. In somevariations, a patient infection state may correspond to a probabilitythat the patient is infected. In some variations, an infectionprobability may correspond to an infection score. For example, a patientinfection state may correspond to the first infection state when aninfection probability is at or above a predetermined threshold (e.g.,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, etc.) and may correspond to thesecond infection state when the infection probability is below thepredetermined threshold or other suitable different threshold (e.g., afirst threshold for infection probability may be used to determine aninfection state, while a second threshold for infection probability maybe used to determine an uninfected state).

In some variations, a patient monitoring device may measure opticalcharacteristics of fluid based on an operating state of a cycler. Forexample, a cycler of a patient monitoring system may perform the stepsof pumping patient fluid into a drain line (drain cycle), then stop thepump such that fluid is static within the drain line during the stepswhen the cycler is pumping fluid into the patient line (infusion cycle)or the cycler is stopped while the fluid is dwelling within the patient(dwell cycle). In some variations, a patient monitoring device mayobtain sensor measurements and analyze the measurements according to theoperating state of the cycler. For example, the sensor measurements maybe performed during a drain cycle of the cycler and OFF during aninfusion cycle and/or a dwell cycle. Additionally or alternatively,optical characteristics of fluid flow in a continuous ambulatoryperitoneal dialysis (CAPD) system may be measured. Additionally oralternatively, different turbidity algorithms may be applied to one ormore of the drain cycle, infusion cycle, and dwell cycle. As describedin more detail herein, methods of estimating a fluid flow rate (e.g.,pump ON/OFF) of a patient fluid may correspond to an operating state ofa cycler. The estimated fluid flow rate may be used to ensure accuratefluid sensing, distinguish fluid properties for each drainage (when thetreatment cycle has more than one drainage), reduce energy consumption,and increase the lifespan of the patient monitoring device. In somevariations, fluid flow rate may comprise a set of fluid flow states. Forexample, a first fluid flow state may comprise a continuous fluid flowthrough a fluid conduit (e.g., continuous fluid pumping through a drainline) and a second fluid flow state may comprise a non-continuous fluidflow through the fluid conduit (e.g., no fluid pumping through a drainline). In some variations, fluid flow rate may comprise a volume offluid passing through a given cross-sectional area per unit time.

Optical measurements of fluid may suffer from discrete sources of noisesuch as bubbles or large particulate matter. In some variations, methodsof detecting a bubble may be performed and allow such signal data to beexcluded so as to increase a signal-to-noise ratio of the opticalmeasurements. Other sources of noise such as fibrin particles, patientbleeding, ascites fluid drainage, and the like may be detected andexcluded from the optical measurements used in fluid analysis.

The systems, devices, and methods described here may be used in avariety of different dialysis therapies to treat kidney failure. Forexample, dialysis therapy may comprise any and all therapies thatutilize fluids (e.g., patient's blood, dialysate) to remove waste,toxins, and excess water from the patient. Such therapies may comprisehemodialysis, hemofiltration, hemodiafiltration (HDF) and peritonealdialysis, including automated peritoneal dialysis, continuous ambulatoryperitoneal dialysis, and continuous flow peritoneal dialysis. Suchtherapies may also comprise, where applicable, both intermittenttherapies and continuous therapies used for continuous renal replacementtherapy. Patients treated with dialysis therapies may comprise patientswith chronic renal failure, as well as those with acute renal failure,whether resulting from renal or non-renal disease.

The terms ‘transparent’, ‘transparency’, and variants thereof are usedthroughout the specification. However, it should be understood thatthese terms do not require complete or 100% transmission of light.

Patient Monitoring System

The patient monitoring systems described herein may be configured tomonitor patient fluid and predict patient infection and/or other patientfluid characteristics. In some variations, the patient monitoring systemmay be configured to provide additional functionality to currentperitoneal dialysis systems. For example, the patient monitoring systemmay comprise a fluid conduit configured to extend a length of one ormore of a drain line, tubing, and catheter. A patient monitoring devicemay be configured to analyze patient fluid in the fluid conduit tomonitor infection, measure turbidity, estimate the composition of thefluid, and/or detect fluid flow, etc. The patient monitoring device mayfurther output the results of the fluid analysis to a patient and/orprovider and enable monitoring of the onset and resolution of aninfection.

In some variations, the patient monitoring systems described herein maycomprise a patient monitoring device (e.g., durable electro-mechanicalsystem) configured to engage with a fluidic component (e.g., vessel,fluid conduit). For example, the fluidic component may comprise adisposable vessel (e.g., fluid conduit, cartridge, drain line, tubing,in-dwelling catheter) and may be configured to removeably engage apatient monitoring device (e.g., housing, holder, optical sensorarrangement, display screen, wireless transmitter, etc.). In somevariations, the patient monitoring device may include at least onesensor and a processor to measure patient fluid and predict patientinfection. The fluidic component may include fluid contacting componentsand the patient monitoring device may include a set of non-fluidcontacting components. The fluidic component may be disposable. Forexample, the fluidic component may be replaced at predeterminedintervals (e.g., daily, weekly) and/or predetermined criteria (e.g.,patient infection event). A disposable fluidic component may, forexample, be useful for short-term use since biofouling within the fluidconduit over time may obfuscate (e.g., cloud) an optical measurementregion, causing inaccurate measurements, and result in an unacceptablenumber of false-positive and/or false-negative patient infectionoutputs. The durable component may provide long-term functionality givenproper maintenance (e.g., cleaning). In some variations, fluidcharacteristics such as optical scatter, optical absorption, attenuationdetection angle, and/or fluid flow rate may be measured in a non-fluidcontact manner using the durable component without separate sensors inthe fluidic component. As a result, manufacture of the fluidic componentmay be simplified for high-volume manufacturing and provided at reducedcost. The durable component may comprise a set of structure, materials,and techniques configured to provide high optical quality for opticalsensor measurement. For example, the durable component may comprise astructure configured to reduce ambient light leakage and refractionwhile being suitable for the draft angle requirements and highermanufacturing tolerances associated with injection molding. In somevariations, the fluidic component may be formed by, for example, one ormore of injection molding, machining, solvent bonding,interference/press fit assembly, ultrasonic welding, and 3D printingtechniques. For example, separate portions of a fluidic component may beinjection molded and attached using a solvent to further reducemanufacturing cost. In some variations, a fluidic component may beintegrated into a drain line set through solvent bonding and/oradhesives to further reduce complexity of the system. Furthermore, thefluidic component may be configured to attach to existing drain linesets to provide additional functionality to existing peritoneal dialysissystems. Additionally or alternatively, a disposable vessel such as acartridge, tubing, catheter, drain line, and the like may comprise anoptically transparent measurement portion as described herein.

FIGS. 3A and 3B are perspective views of a patient monitoring system(300) comprising a first fluid conduit (310), second fluid conduit(320), and patient monitoring device (330). As described in more detailherein, the fluid conduit may be releasably coupled to the patientmonitoring device, and the fluid conduit may be a disposable componentthat is replaced at predetermined intervals. The use of the patientmonitoring device may add only a few simple, additional steps to thesetup procedure of a conventional peritoneal dialysis cycler system foradministration of continuous cycling peritoneal dialysis (CCPD). Forexample, the fluid conduit may be coupled to and released from a drainline and drainage vessel (not shown in FIG. 3) in the same manner as aconventional drain line extension, thus adding no additional setup timefor the patient. Moreover, one or more engagement features of thepatient monitoring device may guide the assembly of the fluid conduitvia interaction with one or more alignment features of the fluid conduit(e.g., rotational and/or depth alignment features) to preventmisalignment, thus reducing patient error and compliance issues. Oncethe fluid conduit is coupled to the patient monitoring device, themeasurement and analysis of the patient fluid may be performed andoutput to the patient's care provider without additional patient action.Removal of the fluid conduit may simply require a reversal of theassembly steps. Accordingly, the patient monitoring device adds numerousquantitative patient monitoring capabilities while being simple andefficient to set up, operate, and maintain.

In some variations, the patient monitoring system (300) may comprise aninput device (e.g., switch, push button, voice command) configured toactivate an optical sensor and/or predict an infection state of thepatient. The patient may initiate optical sensor measurement inconjunction with fluid drainage (e.g., drainage of effluent). Thepatient monitoring device (300) may, for example, be attached to orincorporated with one or more of an IV pole or medical cart. Forexample, the patient monitoring system (300) may be used for theadministration of continuous ambulatory peritoneal dialysis (CAPD).

Additionally or alternatively, one or more components of the patientmonitoring devices described herein may be integrated into otherdevices. FIG. 4A depicts a block diagram of a patient monitoring system(400) comprising a cycler (410), a cycler tubing set drain line (430),and drainage vessel (440). The cycler (410) may comprise a sensor (420)as described herein. In some variations, the cycler (410) may beconfigured to pump patient fluid (e.g., dialysate effluent) into thedrain line (430). The drain line (420) may be fluidly coupled to thedrainage vessel (440). An optical characteristic of the patient fluidflowing through the cycler (410) may be measured by the sensor (420).For example, the sensor (420) may be configured to measure an opticalcharacteristic of an optically transparent measurement portion of adisposable cycler cassette.

In some variations, a cassette for a peritoneal dialysis cycler may beconfigured to allow measurement of an optical characteristic of patientfluid (e.g., dialysate effluent) flowing therethrough. FIG. 25A is aschematic diagram of a tubing set cassette (2500) for use with aperitoneal dialysis cycler. While additional fluid channels aretypically required for infusion and drainage of fluid into the patientfrom multiple fluid sources, for clarity, only a subset of fluidchannels are depicted. The cassette (2500) may comprise an inlet (2510),optical measurement region (2512), first reservoir (2520), secondreservoir (2522), and outlet (2530). The inlet (2510) may be configuredto connect directly to a patient in-dwelling catheter and both receivepatient fluid (e.g., dialysate effluent) and infuse fluid (e.g. freshdialysate) to the in-dwelling catheter and may fluidly couple to thefirst reservoir (2520). The inlet (2510) may comprise a generallyoptically transparent measurement portion (2512) having one more opticalproperties and/or structural characteristics similar to an opticalmeasurement portion of the vessels described herein. In addition to thepatient effluent fluid measurement, the optical measurement region(2512) may be configured to measure the properties of infused fluid(e.g. fresh dialysate) as a method of verifying the quality of the fluid(e.g. cleanliness). In another variation, measurement of the infusedfluid may be used to calibrate the optical measurements using a baselinemeasurement. Thus, a measure optical characteristic of the patient fluidmay include subtraction of the baseline measurement from the measuredoptical signal. This calculation may reduce one or more sources ofmeasurement variability including optical variance of the infused fluid,optical variance of the optical measurement portion (including foulingover time), and variance in the illumination source (e.g., lightintensity) and/or optical sensor (e.g., electrical noise).

FIG. 25B is a schematic cross-section top view diagram of the cassette(2500) depicted in FIG. 25A comprising an optical measurement portion(2512) interface to an optical sensor arrangement (2550) of a peritonealdialysis cycler. The optical sensor arrangement (2550) may comprise aset of illumination sources (2560, 2562) and optical sensors (2570,2572). The optical sensor arrangement (2550) may be configured tomeasure one or more optical characteristics of a patient fluid andprovide for illumination from a plurality of illumination directions. Afirst illumination source (2560) may illuminate an optical measurementportion (2512) in a first illumination direction and a secondillumination source (2562) may illuminate the optical measurementportion (2512) in a second illumination direction orthogonal to thefirst illumination direction. Alternatively, the first illuminationsource may have a first illumination direction that is 180 degree offsetfrom the second illumination direction such that the illuminationsources may direct light in opposite directions. In some variations, thepatient fluid may be illuminated from a plurality of non-parallelillumination directions. For example, the first illumination directionmay have an offset from the second illumination direction of betweenmore than about 0 degrees and about 180 degrees. In some variations, thefirst illumination source (2560) and the second illumination source(2562) may be configured to provide illumination at the same wavelength.

In FIG. 25B, a first optical sensor (2570) and a second optical sensor(2572) may be configured to generate a signal corresponding tomeasurement of an optical characteristic of the illuminated patientfluid. The first and second optical sensors may, for example, bephotodiodes. An optical sensor may be configured to measure one or moreof optical scatter and attenuation detection angle (e.g., absorption,obscuration). For example, the optical sensors may be configured tomeasure a property of illuminated patient fluid at anattenuation/absorption/obscuration angle (about 180 degrees), forwardscattering angles (about >90 degrees about <180 degrees), sidescattering angle (about 90 degrees), and back-scattering angles (about<90 degrees, about ≥0 degrees). In FIG. 25B, the first optical sensor(2570) faces the first illumination source (2560) (the first opticalsensor and the first illumination source are on opposite sides of theoptical measurement portion (2512)), and the second optical sensor(2572) faces the second illumination source (2562) (the second opticalsensor and the second illumination source are on opposite sides of theoptical measurement portion (2512)). Alternatively, the first opticalsensor (2570) may be generally orthogonal to the first illuminationsource (2560), and the second optical sensor (2572) may be generallyorthogonal to the second illumination source (2562). Turbidity of thepatient fluid may be estimated based on measured optical characteristicsand the turbidity equations described in more detail herein.

The cassette may comprise one or more ambient light shielding featuresconfigured to enhance the optical measurement of patient fluid. FIG. 5Adepicts a schematic diagram of a patient monitoring system (500) thatmay be used in, for example, a patient's home. The patient monitoringsystem (500) may comprise a cycler (510), drain line (530), drain lineextension (540), and drainage vessel (550, 560). The cycler (510) maycomprise a sensor (520). In some variations, the cycler (510) may beconfigured to pump patient fluid into the drain line (530). The drainline (530) may be fluidically coupled to the drain line extension (540)and a drainage vessel such as toilet (550) or bag (560) configured toreceive the patient fluid.

In some variations, a sensor (420) may be coupled to a drain lineextending from a cycler (e.g., coupled to a drainage prong of a cassetteof a cycler). For example, FIG. 4B illustrates an exemplaryconfiguration of a patient monitoring system (400) comprising anoptically transparent measurement portion (450), a sensor (420), acycler (410), a cycler tubing set drain line (430), and a drainagevessel (440). For example, an in-dwelling catheter or tubing set maycomprise the optically transparent measurement portion (450), which maybe releasably coupled to one or more of a sensor (420) and a disposablecycler cassette of a cycler (410). For example, the opticallytransparent measurement portion (450) may be disposed along a proximalend of the in-dwelling catheter. An optical characteristic of thepatient fluid flowing through the measurement portion (450) may bemeasured by the sensor (420). In some variations, patient fluid may flowthrough the measurement portion (450) and then the cycler (410). Thecycler (410) may be configured to receive and pump patient fluid (e.g.,dialysate effluent) into the drain line (430). The drain line (420) maybe fluidly coupled to the drainage vessel (440).

FIG. 4C illustrates an exemplary configuration of a patient monitoringsystem (400) comprising an optically transparent measurement portion(450), a sensor (420), a cycler (410), a cycler tubing set drain line(430), and a drainage vessel (440). For example, a tubing set maycomprise the optically transparent measurement portion (450), which maybe releasably coupled to one or more of a sensor (420) and a disposablecycler cassette of a cycler (410). An optical characteristic of thepatient fluid flowing through the measurement portion (450) may bemeasured by the sensor (420). In some variations, patient fluid may flowthrough the cycler (410) and then through the measurement portion (450)coupled in-line with the drain line (430). The drain line (430) may befluidly coupled to the drainage vessel (440).

FIG. 5B depicts a schematic diagram of a patient monitoring system (500)that may be used in, for example, a patient's home. The patientmonitoring system (500) may comprise a catheter or tubing set (570), asensor (520), a cycler (510), a drain line (530), a drain line extension(540), and a drainage vessel (550, 560). The sensor (520) may bereleasably coupled to the tubing set (570) downstream of the cycler(510). In some variations, the cycler (510) may be configured to pumppatient fluid into the drain line (530). The drain line (530) may befluidically coupled to the drain line extension (540) and a drainagevessel such as toilet (550) or bag (560) configured to receive thepatient fluid.

FIG. 5C depicts a schematic diagram of a patient monitoring system (500)that may be used in, for example, a patient's home. The patientmonitoring system (500) may comprise a cycler (510), a sensor (520), anoptically transparent measurement portion (450), a drain line (530), adrain line extension (540), and a drainage vessel (550, 560). The sensor(520) may be releasably coupled to the optically transparent measurementportion (450), downstream of the cycler (510). In some variations, theoptically transparent measurement portion (450) may be coupled with thedrain line extension (540) as a continuous fluidic path, as shown inFIG. 5D.

Patient Monitoring Device

The patient monitoring devices described here may be configured tomonitor patient fluid and predict patient infection and/or othercharacteristics of the patient fluid. For example, the patientmonitoring device may be configured to optically measure one or morecharacteristics of patient fluid flowing through a fluid conduit coupledto the patient monitoring device. Furthermore, the patient fluid in thefluid conduit may be analyzed to monitor infection, measure turbidity,estimate the composition of the fluid, and detect fluid flow. Thepatient monitoring device may further output the results of the fluidanalysis to a patient and/or provider and enable monitoring of the onsetand resolution of an infection. In some variations, the patientmonitoring devices described herein may be configured for use in adialysate infusion system or may comprise a stand-alone point-of-carefluid sample analysis device. For example, in some variations, a fluidvessel may be configured as a vial to hold a static, predeterminedvolume of fluid for analysis using the patient monitoring device.Furthermore, in some variations, the patient monitoring device may beconfigured to compactly fit on a surface (e.g., table, desk) and be usedto analyze a patient fluid using any of the methods described herein.For example, the patient monitoring device need not comprise a base(e.g., stand) to reduce a volume of the device.

FIG. 6 depicts a block diagram of a patient monitoring device (600)comprising a sensor arrangement (610), display (620), controller (630),communication device (640), and power source (650). The opticalarrangement (610) may comprise an optical source (612) (e.g.,illumination source) and an optical sensor (614). The optical source(612) may be configured to illuminate patient fluid within a vesseland/or fluid conduit. The optical sensor (614) may be configured tomeasure an optical characteristic of the illuminated patient fluid. Thecontroller (630) may comprise a processor (632) and memory (634)configured to process, analyze, and/or store the measured signal data,determine when the flow is indicative of a drainage cycle, and used tofurther determine when to measure the patient fluid. For example, thecontroller (630) may be configured to generate patient data based atleast in part on a signal measured by the optical sensor (614). Thepatient data may comprise, for example, an infection state (e.g.,probability of infection).

FIG. 7A depicts a semi-transparent perspective view of a patientmonitoring device (700). FIG. 7B depicts an exploded schematic diagramof the patient monitoring device (700) comprising a housing (702) (e.g.,enclosure), base (e.g., stand) (704), optical sensor arrangement (710),display (720), controller (730), communication device (740) (e.g.,antenna, LTE or other cellular modem), and holder (750) (e.g., fluidconduit interface). The patient monitoring device (700) may be compactenough to fit on a table or nightstand. In some variations, the base(704) may elevate the housing (702) above a resting surface. That is,the housing (702) may be offset and spaced apart from the base (704).The spacing between the housing (702) and base (704) may, for example,allows sufficient room for one or more of a fluid conduit (e.g., drainline) and a disposable vessel (e.g., drainage bag) to be positionedunderneath the housing (702) as shown in FIGS. 8A, 8B, and 9B. Theoffset maybe, for example, between about 5 cm and about 30 cm.

FIGS. 7C and 7D depict a perspective view of the patient monitoringdevice (700) with the housing (702) in an open configuration. A vessel(750) is removeably held within the housing (702) and aligned to theoptical sensor arrangement (710). FIG. 7D illustrates the vessel (750)coupled to a first fluid conduit (760) and a second fluid conduit (762)and FIG. 7C depicts the vessel (750) without the fluid conduit (760) forthe sake of clarity. As described in more detail herein, the vessel(750) and housing (702) may comprise a set of mating features configuredto orient relative rotation and/or depth of the vessel (750) and housing(702) to each other such that the vessel (750) may be inserted into thehousing (702) in a single direction, depth, and orientation.

FIGS. 8A-8D depict various views of a variation of the patientmonitoring device (800). The patient monitoring device (800) maycomprise a housing (810), holder (820), display (850), and stand (860).A fluid conduit (830) may be fluidly coupled to an outlet of a cyclertubing set drain line (840). The fluid conduit (830) may be engaged tothe holder (820), as described in more detail herein. As shown in FIG.8B, the base (860) may be offset and spaced apart from the housing (810)to allow the fluid conduit (830) to be elevated relative to the drainline (840). For example, the fluid conduit (830) may be heldsubstantially vertically to promote de-airing of the fluid conduit (830)during one or more of priming and fluid flow, thus reducing the presenceof bubbles in an optical measurement portion of the fluid conduit (830)during measurement. In particular, the fluid conduit may be routed suchthat fluid is configured to flow in a low-to-high direction (i.e.,generally upwards) that follows a direction of air buoyancy thatpromotes de-airing of the fluid conduit (830).

FIGS. 8A and 8D depict the patient monitoring device (800) in alight-shielding door closed configuration, and FIGS. 8B and 8C depictthe patient monitoring device (800) in a light-shielding door openconfiguration. The housing (810) may be configured to transition betweena door closed configuration (FIGS. 8A, 8D) and a door open configuration(FIGS. 8B, 8C). In the door closed configuration, the housing (810) anddoor (811) may form an ambient light seal configured to reduce ambientlight penetration into an optical measurement region of the fluidconduit (830). In some variations, the housing (810) may furthercomprise a door (811) and a hinge (812) configured to open and close thehousing (810). The door (811) in the closed configuration may form atop, bottom, and sidewall portion of the light seal. For example, thedoor (811) may enclose the outlet of a drain line (840) to form a bottomportion of the light seal that reduces ambient light penetration throughthe drain line (840). FIG. 8C is a side view of the patient monitoringdevice (800) in the door open configuration. The door (811) may beconfigured to enclose a portion of a cap (834) to form a top portion ofthe light seal. The door (811) may comprise an alignment feature wherethe door (811) may be configured to fully close only when the cap (834)is fully inserted and engaged in the holder (820). For example, in somevariations, one or more alignment features in the door (811) and/or thevessel (832) or cap (834) may be arranged such that the door may fullyclose only if the vessel (832) and cap (834) are correctly oriented in asingle predetermined orientation, thereby providing confirmation thatthe vessel and cap are in the correct orientation. Once the vessel (832)is engaged with the holder (820) in a predetermined orientation relativeto the holder (820), the closed door (811) may prevent the cap (834) andvessel (832) from moving vertically (or being lifted out of the housing(810)), and the alignment features of the holder (820) will prevent thevessel (832) from being rotated, tilted, repositioned laterally, orpushed downward.

As shown in FIG. 8D, the door (811) may comprise a switch (e.g., latch,handle) (813) configured to allow a patient to open and securely closethe door (811). For example, the switch (813) may comprise aspring-loaded mechanism and/or magnets. In some variations, the door(811) and/or other portion of the housing may comprise a sensor (e.g.,Hall effect sensor, switch, contact sensor, optical-based sensor, etc.)configured to generate a door signal indicating an open/close state ofthe housing (810).

FIGS. 9A-9C depict various views of a patient monitoring device (900).The patient monitoring device (900) may comprise a housing (910), door(911), hinge (912), holder (920), slot (924), optical sensor (926),display (950), and stand (960). A fluid conduit (930) may be fluidlycoupled to the outlet of a drain line (940), as shown in FIG. 9B. Thefluid conduit (930) may comprise a vessel (932) and a cap (934). FIGS.9A and 9B depict the patient monitoring device (900) in an openconfiguration. FIG. 9C depicts a patient monitoring device (900′)similar to the device (900) shown in FIGS. 9A and 9B except for thelocation of tubing routing portion (922′). Patient monitoring device(900′) is shown in a closed configuration.

FIGS. 10A and 10E are perspective views of a holder (1010) of a patientmonitoring device (1000) configured to receive and engage a portion of afluid conduit (e.g., vessel) (not shown for the sake of clarity) in apredetermined orientation relative to at least one set of illuminationsources (1040) and at least one set of optical sensors (1050). Theillumination sources (1040) may be configured to illuminate the receivedportion of the fluid conduit and the optical sensors (1050) may beconfigured to generate a signal such as an optical characteristicmeasurement based on illuminated patient fluid. FIGS. 10B and 10Cillustrate an optical sensor arrangement comprising an illuminationhousing (1011), collimator (1032), lens (1030) (e.g., aspherical lens),lens-locating O-rings (1033), and illumination sources (1042, 1044,1046). The illumination housing (1011) may define a set of apertures(1013).

The holder (1010) may define a cavity (1002) having a generallyrectangular (e.g., square) cross-sectional shape configured to receive aportion of the fluid conduit having a generally rectangular (e.g.,square) cross-sectional shape. The holder (1010) may further define anengagement feature (1012) (e.g., slot, slit) configured to orient thereceived portion of the fluid conduit in a predetermined rotationalorientation relative to the illumination source (1040) and opticalsensor (1050). For example, the engagement feature (1012) may define anopen slot that may extend along a longitudinal axis of the holder (1010)(see FIG. 10E) and located at an edge of the generally rectangularcross-sectional shape. The slot may allow one or more of the vessel,fluid conduit, and drain line to be assembled and removed from theholder (1010) without disconnecting any of the drain line components.The engagement feature (1012) may encourage or ensure one-way insertionof the fluid conduit into the holder (1010). In some variations, asfurther described herein, the holder (1010) may additionally oralternatively comprise a second engagement feature (e.g., shoulder, lip,protrusion, etc.) configured to orient the received portion of the fluidconduit at a predetermined at a depth position relative to theillumination source (1040) and optical sensor (1050).

FIG. 26 is an exploded perspective view of a vessel (2610) disposed in aholder (2620) of a patient monitoring device (2600). The holder (2620)may comprise an engagement portion (2622) such as a slot that extendsalong a longitudinal axis of the holder (2620). The holder (2620) may beconfigured to couple to one or more portions of a housing (2630) of thepatient monitoring device (2600). An optical sensor arrangement (2640)may be coupled to the holder (2620). To remove the vessel (2610) fromthe holder (2620), a CCPD tubing set including a drain line and/or fluidconduit (not shown) coupled to the vessel (2610) may be lifted up fromthe holder (2620) and moved laterally through the slot (2622) withoutdisconnecting any component of the tubing set.

As shown in the perspective views of FIGS. 12A and 12B, a holder (1200)may be configured to releasably receive a portion of a vessel (1250).The vessel (1250) may comprise a rotational alignment feature (1252)configured to engage an engagement feature (1230) (e.g., slot, slit) ofthe holder (1200) such that the vessel (1250) is secured androtationally aligned to the holder (1200) in a single position. Forexample, the engagement feature (1230) may be configured to orient thereceived portion of the fluid conduit (1250) by mating with thealignment feature (1252) of the received portion of the fluid conduit(1250). Additionally or alternatively, the vessel (1250) may comprise adepth alignment feature configured to engage a second engagement featuresuch that the vessel (1250) is positioned a predetermined depth, asdescribed in further detail below.

For example, in some variations, the alignment feature (1252) maycomprise a protrusion having a shape configured to form an interferencefit with the engagement feature (1230) of the holder (1200). Thealignment feature (1252) may comprise a taper that allows the vessel(1250) to slide and/or self-align into the engagement feature (1230).FIG. 12B is a perspective view of the holder (1200) and vessel (1250)from a vantage point opposite that of FIG. 12A. The sidewalls of theholder (1200) shown in the foreground of FIG. 12B do not comprise acorresponding engagement feature (1230). Therefore, the shape of thevessel (1250), alignment feature (1252), holder (1200), and engagementfeature (1230) encourages the patient to insert and rotationally alignthe vessel (1250) in a single orientation such that the vessel (1250)may be aligned to the illumination sources (1210) and optical sensors(1220).

In some variations, the alignment feature (1252) may further comprise adepth alignment feature such as a set of one or more shoulders (1253)(e.g., lip, protrusions) configured to contact the sidewalls of theholder (1200) and aid depth alignment of the vessel (1250) to the holder(1200). The shoulders (1253) may be disposed at least widthwise alongone or more sidewalls of the vessel (1250). The holder (1200) may beconfigured to provide a light seal around the vessel (1250) except forthe open top portion, open bottom portion, and open portion of theengagement feature (1230). For example, the holder (1200) may comprisean opaque gasket or other seal that substantially blocks ambient light.A door of the patient monitoring device and light seal features of thevessel (1253) may further contribute to sealing the vessel (1250) fromambient light.

In some variations, the patient monitoring device may comprise a set ofone or more fluid conduit routing features configured to aid opticalmeasurement of the fluid conduits. As shown in FIG. 8A, the outlet of adrain line (840) may be routed beneath the housing (810) such that aportion of the fluid conduit (830) is held substantially orthogonal tothe base (860). In some variations, a portion of the fluid conduit (830)distal to the vessel (832) may form a loop above or around the housing(810) and be releasably coupled to a routing portion (822) configured toprovide strain relief, reduce downstream kinking of the fluid conduit(830), and/or reduce blockages in the fluid conduit (830).

In FIGS. 8B and 8C, the routing portion (822) may comprise a channel ofthe housing (810) through which the fluid conduit (830) may be held. InFIGS. 9B and 9C, the routing portion (922) may define an external slotconfigured to releasably couple to the fluid conduit (930). For example,a portion of the fluid conduit (930) may be slid or clipped into therouting portion (922). The routing portion (922) may be provided on anysuitable side of the housing (910). For example, as shown in FIG. 9B,the routing portion (922) may be along a rear side of the housing, whileas shown in FIG. 9C, the routing portion (922′) may be along a lateralside of the housing.

In some variations, the routing portion may further comprise one or morefastening features to laterally, axially, and/or rotationally fix (orotherwise secure) the fluid conduit into the routing portion. Forexample, a routing portion may comprise a channel that is sized toreceive the fluid conduit with an interference fit (e.g., snap fit). Asanother example, a routing portion may include one or more fasteningdevices (e.g., clip, snap, band, etc.) to secure the fluid conduit inthe channel. Similarly, a routing portion may include a channel havingone or more loops or other structure spanning the slot (or otherlattice) through which the fluid conduit may be fed into the channel. Asanother example, a routing portion may include a channel havingtexturing (e.g., bumps, rings) along its surface to increase frictionbetween the channel and the fluid conduit. As another example, adhesiveon the channel and/or fluid conduit may be used to mount the fluidconduit within the channel. Any of the above-described examples offastening features may be combined in any suitable manner.

In some variations, the patient monitoring device may comprise anoptical sensor arrangement configured to illuminate patient fluid andmeasure optical characteristics of the patient fluid. For example, theoptical sensor arrangement may comprise an illumination source and anoptical sensor. In some variations, sets of illumination sources andoptical sensors may be arranged in parallel and configured to measureoptical characteristics of different regions of a vessel. Non-limitingexamples of an illumination source (e.g., light source) includeincandescent, electric discharge (e.g., excimer lamp, fluorescent lamp,electrical gas-discharge lamp, plasma lamp, etc.), electroluminescence(e.g., light-emitting diodes, organic light-emitting diodes, laser,etc.), induction lighting, and fiber optics. In some variations, theoptical sensor may comprise a photodiode, charged coupled device (CCD)or complementary metal-oxide semiconductor (CMOS) optical sensor.

FIGS. 14A and 14B are schematic diagrams of a cross-section (e.g.,single planar arrangement) of an optical sensor arrangement. The opticalsensor arrangement may provide for illumination from a plurality ofillumination directions. As shown in FIG. 14A, a first illuminationsource (1410) may illuminate a vessel (1430) in a first illuminationdirection and a second illumination source (1412) may illuminate thevessel (1430) in a second illumination direction orthogonal to the firstillumination direction. In another example shown in FIG. 14B, the firstillumination source (1410) may have a first illumination direction thatis 180 degree offset from the second illumination direction such thatthe illumination sources may direct light in opposite directions. Insome variations, the patient fluid may be illuminated from a pluralityof non-parallel illumination directions. For example, the firstillumination direction may have an offset from the second illuminationdirection of between more than about 0 degrees and about 180 degrees. Insome variations, the first illumination source (1410) and the secondillumination source (1412) may be configured to provide illumination atthe same wavelength.

In FIGS. 14A and 14B, a first optical sensor (1420) and a second opticalsensor (1422) may be configured to generate a signal corresponding tomeasurement of an optical characteristic of the illuminated patientfluid. The first and second optical sensors may, for example, bephotodiodes. An optical sensor may be configured to measure one or moreof optical scatter and attenuation detection angle (e.g., absorption,obscuration). For example, the optical sensors may be configured tomeasure a property of illuminated patient fluid at anattenuation/obscuration angle (about 180 degrees), forward scatteringangles (about >90 degrees about <180 degrees), side scattering angle(about 90 degrees), and back-scattering angles (about <90 degrees, about≥0 degrees). In FIG. 14A, the first optical sensor (1420) faces thefirst illumination source (1410) (the first optical sensor and the firstillumination source are on opposite sides of the vessel (1430)), and thesecond optical sensor (1422) faces the second illumination source (1412)(the second optical sensor and the second illumination source are onopposite sides of the vessel (1430)). In FIG. 14B, the first opticalsensor (1420) is generally orthogonal to the first illumination source(1410), and the second optical sensor (1422) is generally orthogonal tothe second illumination source (1412).

In some variations, an optical sensor arrangement may comprise aplurality of planar arrangements such as that shown in FIGS. 14A and14B. For example, as shown in FIGS. 10D and 10E, a plurality ofillumination sources (1040) and optical sensors (1050) may be coupled tothe holder (1010). The holder (1010) may be coupled to three planararrangements of illumination sources and optical sensors. In somevariations, the planar sets may be spaced apart and parallel to alongitudinal axis of the holder (1010). In some variations, theillumination sources (1040) may be configured to output the same ordifferent wavelengths. For example, two or more illumination sources(1040) may be configured to output the same wavelengths to provideredundancy and improve the accuracy of the optical measurements. Asanother example, two or more illumination sources (1040) may beconfigured to output different wavelengths, where measurementsassociated with different wavelengths may provide different information(e.g., may allow identification of different particle types associatedwith each respective wavelength).

FIG. 10F illustrates an optical sensor arrangement comprising acollimator (1032), at least one lens (1030) (e.g., aspherical lens), andillumination sources (1042, 1044, 1046). In some variations, anillumination source (1042, 1044, 1046) and/or collimator (1032) may beconfigured to minimize stray light received by the optical sensorarrangement. For example, one or more of an illumination source and theoptical sensor arrangement (e.g., collimator) may comprise one or moreof an anti-reflective coating and light trap. For any of the opticalsensor arrangements described herein, the aperture may additionally oralternatively be configured to allow a predetermined range of viewingangles of the optical sensor arrangement.

As shown in FIG. 10C, a first illumination source (1042) may beconfigured to emit light at a first wavelength between about 800 nm andabout 900 nm (e.g., about 860 nm). A second illumination source (1044)may be configured to emit light at a second wavelength between about 400nm and about 450 nm (e.g., about 405 nm). A third illumination source(1046) may be configured to emit light at a third wavelength betweenabout 500 nm and about 550 nm (e.g., about 525 nm). The firstillumination source (1042) may be placed in a generally centrallocation, furthest away from any potential sources of ambient lightleakage (e.g., from the inlet and outlet of the vessel). The secondillumination source (1044) may be placed nearest to an outlet of thevessel to minimize alterations to the patient fluid due to theillumination at the second wavelength (e.g., UV light). Additionally oralternatively, two of the illumination sources may be configured tooutput illumination at the same wavelength. In some variations, a fourthillumination source (not shown) may be configured to emit light at afourth wavelength between about 230 nm and about 290 nm.

In some variations, the illumination source may comprise one or more ofa light emitting diode (and/or laser, scintillator or other lightsource), collimator, and lens. The illumination source may, in somevariations, further include one or more filters. In some variations, oneor more components, such as the collimator, may include ananti-reflective coating and/or other suitable feature to minimize straylight output from the illumination source. At least some of thesecomponents may be arranged relative to each other via a mounting blockor other fixture. For example, the illumination source may comprise aconvex-plano lens configured to collimate the illumination and a set offilters configured to narrow a wavelength range. FIGS. 10B and 10Cillustrate an illumination housing (1011) comprising a lens (1030) andcollimator (1032).

In some variations, the lens (1030) may comprise a convex-plano oraspherical lens. In some variations, each illumination source of eachplanar arrangement may have a respective set of at least a collimatorand a lens.

FIG. 11A is a side view of an optical sensor arrangement (1100) of apatient monitoring device comprising a set of substantially orthogonalillumination sources (1110) and corresponding optical sensors (1120).The illumination sources (1110) are orthogonal to the optical sensors(1120). FIG. 11A depicts a pair of orthogonal illumination sources(1110) and a pair of orthogonal optical sensors (1120) on each of threesubstantially parallel cross-sectional planes. The optical sensorarrangement (1100) may comprise a lens (1112). A vessel (1150) may bealigned to the optical sensor arrangement (1100) so as to receiveillumination from the illumination source (1110). FIG. 11B is across-sectional view one plane of the optical sensor arrangement (1100)depicted in FIG. 11A along the A-A line having exemplary dimensions. Forexample, the illumination source (1110) may have width of about 5mm. Alens (1112) may have a thickness of about 10 mm. The optical sensor(1120) may have an aperture of about 5 mm with an aperture distance ofabout 4 mm (e.g., 4.11 mm). However, the optical sensor arrangement mayinclude other suitable dimensions.

In some variations, an optical sensor arrangement may comprise at leastone illumination source configured to emit white light at a widespectrum (e.g., between about 200 nm and about 1400 nm) and/or emitlight in different wavelength ranges. For example, the illuminationsource may comprise an RGB light emitting diode. The optical sensorarrangement may further comprise at least one optical sensor configuredto measure optical characteristics of illuminated patient fluid. Forexample, the optical sensor may comprise a spectrophotometer to measureabsorbance or scatter across a wide range of wavelengths.

In some variations, an optical sensor arrangement may be configured toat least partially compensate for refraction of an optical measurementregion such as a vessel. FIG. 13 is a schematic diagram of opticalrefraction of illumination (1302) through a vessel (1310). As describedin more detail herein, the vessel (1310) may comprise an opticallytransparent measurement portion and a set of substantially planarsurfaces (e.g., sidewalls). The vessel (1310) may comprise a taper(e.g., draft angle), such as to help facilitate injection molding orsimilar manufacturing processes, or to help self-align the vessel (1310)in the mating taper geometry of a holder. In FIG. 13, illumination(1302) generated by illumination source (1320) undergoes refraction atangles θ₁, θ₂, θ₃, and θ₄, as the illumination (1302) travels throughthe vessel (1310) and patient fluid (1312). As such, the illumination(1302) does not propagate through the vessel (1310) in a straight lineout of the illumination source (1320). As shown in FIG. 13, an opticalsensor (1330) may be positioned to compensate for this refraction tomaximize the received illumination (1302) and thus improve asignal-to-noise ratio. For example, an axial position of an opticalsensor (1330) substantially opposite the illumination source (1320)across the vessel (1310) may be slightly offset from the axial positionof the illumination source (1320) by a distance (D) in the direction ofthe refraction. In some variations, the offset distance (D) may, forexample, be between about 0.1 mm and about 1 cm. In addition, theoptical sensor (1330) may be slightly tilted from to plane of theillumination source (1320) by a predetermined tilt angle. In somevariations, the tilt angle may, for example, be between about 0.1degrees and about 5 degrees.

In some variations, the thickness of an optical measurement region ofthe vessel may vary in order to reduce refraction and/or the effectsthereof. For example, a thickness of at least a portion of the opticalmeasurement region may be thinner than an inlet and outlet of thevessel. As another example, the thickness of at least a portion of theoptical measurement gradually decrease in the direction of the expectedrefraction, to counter or compensate for the expected refraction.

In some variations, a reduction in measured light intensity due torefraction may be determined (e.g., empirically) for each optical sensorand expressed as a refraction constant and/or coefficient. For example,an estimated turbidity based on the measured optical characteristics maybe calibrated by a known refraction factor.

In some variations, the patient monitoring device may comprise anambient light sensor configured to measure ambient light of theenvironment external to the housing. For example, an ambient lightsensor may be disposed on an outer surface of the housing (e.g.,adjacent to a display or on a top portion of the housing).

In some variations, the patient monitoring device may comprise a tiltsensor configured to measure an angle of the patient monitoring devicerelative to ground. An operation of the patient monitoring device may beinterrupted in response to detection of tilt, due to the potentialtrapping of air bubbles when tilted excessively, resulting in inaccuratesensor measurements. Furthermore, a patient may be instructed to orientthe patient monitoring device in an upright position. The tilt sensormay comprise an accelerometer, gyroscope, IMU, etc.

In some variations, the patient monitoring device may comprise a fluidconduit sensor configured to detect the presence of a fluid conduitand/or vessel in the holder of the patient monitoring device. The fluidconduit sensor may comprise an optical sensor.

In some variations, the patient monitoring device may comprise one ormore optical sensors used to determine if the optical sensor arrangementshould be cleaned, serviced, and/or replaced. For example, an opticalsensor may be configured to measure light intensity of the illuminationsource when the holder is empty (e.g., no vessel or fluid conduit isbetween the optical sensor and illumination source) as a baselineoptical measurement. The patient may be notified to clean the opticalsensor arrangement if the measured light intensity is below apredetermined threshold. If after cleaning (e.g., wiping down) theillumination source and optical sensor, the measured light intensity isstill below the predetermined threshold, then the patient may benotified (e.g., on the display) that the patient monitoring deviceshould be serviced and/or replaced. In some variations, the one or moreoptical sensors may be the same or different from the optical sensorsused to measure optical characteristics of patient fluid.

Output Device

As described above, the patient monitoring device may comprise one ormore output devices, such as a display. In some variations, a displaymay comprise a graphical user interface configured to permit a patientto view information and/or control a patient monitoring device. In somevariations, the display may be angled upward towards the patient to aidusability and visualization. In some variations, a display may compriseat least one of a light emitting diode (LED), liquid crystal display(LCD), electroluminescent display (ELD), plasma display panel (PDP),thin film transistor (TFT), organic light emitting diodes (OLED),electronic paper/e-ink display, laser display, and/or holographicdisplay.

FIG. 15 is a set of illustrative variations of a graphical userinterface (GUI) that may be displayed on a patient monitoring device.The GUIs permit a patient to view one or more of setup messages, devicestatus, patient status, patient instructions, error messages, and thelike. A set of one or more setup GUIs may instruct a patient how tooperate the patient monitoring device. A first GUI (1500) may comprisean initialization message such as a startup message. A second GUI (1502)may comprise a connection message. For example, a patient may beinstructed to engage a vessel to the patient monitoring device. A thirdGUI (1504) may comprise a seal message. For example, a patient may beinstructed to close a door to form a light seal around a vessel. Afourth GUI (1506) may comprise a cleaning message. For example, apatient may be instructed to clean the patient monitoring device atperiodical intervals.

A set of one or more patient status GUIs may inform the patient of aninfection state. A fifth GUI (1508) may comprise a positive infectionmessage. For example, a patient may be notified of an infection andinstructed to call their provider. In some variations, a positiveinfection message may be displayed in a different color (e.g., orange,red, yellow). For example, a positive infection message may becolor-coded based on severity of infection score (as described infurther detail below). In some variations, the patient monitoring devicemay transmit a positive infection message to a provider. The positiveinfection message may, for example, include an infection scoredetermined by the system (as described in further detail below). A sixthGUI (1510) may comprise negative infection message. For example, thepatient may be notified that the patient monitoring device is monitoringthe patient fluid and otherwise operating normally.

A set of one or more device status GUIs may inform the patient of thestatus of the patient monitoring device. A seventh GUI (1512) maycomprise a communication message. For example, a patient may be notifiedthat the patient monitoring device does not form a network connection(e.g., for transmitting patient data). An eighth GUI (1514) may comprisea tilt message. For example, a patient may be instructed to orient thepatient monitoring device in an upright position. A ninth GUI (1516) maycomprise an error message. For example, a patient may be notified of afailure of at least one component of the patient monitoring device suchthat the device should be replaced. A failure may, for example, includereduced performance of an illumination source and/or optical sensorbelow a predetermined threshold.

In some variations, the data may be processed and analyzed on a remotecomputing device (e.g., remote server) and the results output to apatient's smartphone through a set of GUIs. Additionally oralternatively, the patient monitoring device may comprise an opticalwaveguide (e.g., light pipe, light distribution guide, etc.) to allow apatient to visualize an infection state. One or more optical waveguidesmay receive light from a light source (e.g., illumination source) usinga predetermined combination of light output parameters (e.g.,wavelength, frequency, intensity, pattern, duration) to output aninfection state. In some variations, the optical waveguide may be formedintegral with the housing of the patient monitoring device to simplifymanufacturing and allowing for a compact design and minimal power usage.

An optical waveguide may refer to a physical structure that guideselectromagnetic waves such as visible light spectrum waves to passivelypropagate and distribute received electromagnetic waves. Non-limitingexamples of optical waveguides include optical fiber, rectangularwaveguides, light tubes, light pipes, combinations thereof, or the like.For example, light pipes may comprise hollow structures with areflective lining or transparent solids configured to propagate lightthrough total internal reflection. The optical waveguides describedherein may be made of any suitable material or combination of materials.For example, in some variations, the optical waveguide may be made fromoptical-grade polycarbonate. In some variations, the housings asdescribed herein may be co-injected molded to form the opticalwaveguides. In other variations, the optical waveguides may be formedseparately and coupled to the housing. In some variations, the opticalwaveguides described herein may comprise one or more portions configuredto emit light. For example, at least one of the portions may compriseone or more shapes. For example, the optical waveguide may follow theedges of the housing and/or form a shape of a logo. In some variations,the optical waveguides described herein may comprise a surface contourincluding, for example, a multi-faceted surface configured to increasevisibility from predetermined vantage points.

The light patterns described herein may, for example, comprise one ormore of flashing light, occulting light, isophase light, etc., and/orlight of any suitable light/dark pattern. For example, flashing lightmay correspond to rhythmic light in which a total duration of the lightin each period is shorter than the total duration of darkness and inwhich the flashes of light are of equal duration. Occulting light maycorrespond to rhythmic light in which the duration of light in eachperiod is longer than the total duration of darkness. Isophase light maycorrespond to light which has dark and light periods of equal length.Light pulse patterns may include one or more colors (e.g., differentcolor output per pulse), light intensities, and frequencies.

In some variations, the patient monitoring device may comprise an inputdevice (e.g., touch screen). Some variations of an input device maycomprise at least one switch configured to generate a control signal.For example, an input device may comprise a touch surface for a user toprovide input (e.g., finger contact to the touch surface) correspondingto a control signal. An input device comprising a touch surface may beconfigured to detect contact and movement on the touch surface using anyof a plurality of touch sensitivity technologies including capacitive,resistive, infrared, optical imaging, dispersive signal, acoustic pulserecognition, and surface acoustic wave technologies. In variations of aninput device comprising at least one switch, a switch may comprise, forexample, at least one of a button (e.g., hard key, soft key), touchsurface, keyboard, analog stick (e.g., joystick), directional pad,mouse, trackball, jog dial, step switch, rocker switch, pointer device(e.g., stylus), motion sensor, image sensor, and microphone. A motionsensor may receive user movement data from an optical sensor andclassify a user gesture as a control signal. A microphone may receiveaudio data and recognize a user voice as a control signal.

In some variations, the patient monitoring device may comprise an outputdevice such as an audio device and/or haptic device. For example, anaudio device may audibly output patient data, fluid data, infectiondata, system data, alarms and/or notifications. For example, the audiodevice may output an audible alarm when an infection is predicted and/orwhen a drain line blockage is detected. In some variations, an audiodevice may comprise at least one of a speaker, piezoelectric audiodevice, magnetostrictive speaker, and/or digital speaker. In somevariations, a patient may communicate with other users using the audiodevice and a communication channel. For example, a user may form anaudio communication channel (e.g., cellular call, VoIP call) with aremote provider.

In some variations, a haptic device may be incorporated into the patientmonitoring device to provide additional sensory output (e.g., forcefeedback) to the patient. For example, a haptic device may generate atactile response (e.g., vibration) to confirm user input to an inputdevice (e.g., touch surface).

Network

In some variations, the systems and methods described herein may be incommunication with other computing devices via, for example, one or morenetworks, each of which may be any type of network (e.g., wired network,wireless network). The communication may or may not be encrypted. Awireless network may refer to any type of digital network that is notconnected by cables of any kind. Examples of wireless communication in awireless network include, but are not limited to cellular, radio,satellite, and microwave communication. However, a wireless network mayconnect to a wired network in order to interface with the Internet,other carrier voice and data networks, business networks, and personalnetworks. A wired network is typically carried over copper twisted pair,coaxial cable and/or fiber optic cables. There are many different typesof wired networks including wide area networks (WAN), metropolitan areanetworks (MAN), local area networks (LAN), Internet area networks (IAN),campus area networks (CAN), global area networks (GAN), like theInternet, and virtual private networks (VPN). Hereinafter, networkrefers to any combination of wireless, wired, public and private datanetworks that are typically interconnected through the Internet, toprovide a unified networking and information access system.

Cellular communication may encompass technologies such as GSM, PCS, CDMAor GPRS, W-CDMA, EDGE or CDMA2000, LTE, WiMAX, and 3G, 4G, and/or 5Gnetworking standards. Some wireless network deployments combine networksfrom multiple cellular networks or use a mix of cellular, Wi-Fi, andsatellite communication.

Controller

Generally, the patient monitoring devices described here may comprise acontroller comprising a processor (e.g., CPU) and memory (which caninclude one or more non-transitory computer-readable storage mediums).The processor may incorporate data received from memory and over acommunication channel to control one or more components of the system.The memory may further store instructions to cause the processor toexecute modules, processes and/or functions associated with the methodsdescribed herein. In some variations, the memory and processor may beimplemented on a single chip. In other variations, they can beimplemented on separate chips. Additionally or alternatively, one ormore controllers (e.g., one or more processors and memory) may bedisposed separate from the patient monitoring devices described herein.For example, a patient monitoring device comprising a first controllermay be configured to transmit and receive data wirelessly (using acommunication device) to a server comprising a second controller. Any ofthe data processing methods described herein may be performed by one ormore of the controllers described herein.

A controller may be configured to receive and process signal data froman optical sensor and other data (e.g., patient data, fluid data) fromother sources (e.g., computing device, database, server, provider, userinput). The patient monitoring device may be configured to receive,process, compile, store, and access data. In some variations, thepatient monitoring device may be configured to access and/or receivedata from different sources. The patient monitoring device may beconfigured to receive data directly input and/or measured from apatient. Additionally or alternatively, patient monitoring device may beconfigured to receive data from separate devices (e.g., a smartphone,tablet, computer) and/or from a storage medium (e.g., flash drive,memory card). The patient monitoring device may receive the data througha network connection, as discussed in more detail herein, or through aphysical connection with the device or storage medium (e.g. throughUniversal Serial Bus (USB) or any other type of port). The patientmonitoring device may be in communication with a computing device thatmay include any of a variety of devices, such as a cellular telephone(e.g., smartphone), tablet computer, laptop computer, desktop computer,portable media player, wearable digital device (e.g., digital glasses,wristband, wristwatch, brooch, armbands, virtual reality/augmentedreality headset), television, set top box (e.g., cable box, videoplayer, video streaming device), gaming system, or the like.

The patient monitoring device may be configured to receive various typesof data. For example, the patient monitoring device may be configured toreceive a patient's personal data (e.g., gender, weight, birthday, age,height, diagnosis date, anniversary date using the device, etc.), apatient's fluid data, general health information of other similarlysituated patients, or any other relevant information. In somevariations, the patient monitoring device may be configured to create,receive, and/or store patient profiles (and/or may be in communicationwith one or more suitable memory devices for creating, receiving and/orstoring the same). A patient profile may contain any of the patientspecific information previously described. While the above mentionedinformation may be received by the patient monitoring device, in somevariations, the patient monitoring device may be configured to processany data from information it has received using software stored on thedevice itself, or externally. In another variation, the patientmonitoring device may be paired (wired or wirelessly) to other patientmonitoring devices (e.g., pulse oximeter, blood pressure monitor)configured to measure one or more patient parameters.

The processor may be any suitable processing device configured to runand/or execute a set of instructions or code and may include one or moredata processors, image processors, graphics processing units, physicsprocessing units, digital signal processors, and/or central processingunits. The processor may be, for example, a general purpose processor,Field Programmable Gate Array (FPGA), an Application Specific IntegratedCircuit (ASIC), and/or the like. The processor may be configured to runand/or execute application processes and/or other modules, processesand/or functions associated with the system and/or a network associatedtherewith. The underlying device technologies may be provided in avariety of component types (e.g., metal-oxide semiconductor field-effecttransistor (MO SFET) technologies like complementary metal-oxidesemiconductor (CMOS), bipolar technologies like emitter-coupled logic(ECL), polymer technologies (e.g., silicon-conjugated polymer andmetal-conjugated polymer-metal structures), mixed analog and digital,and/or the like.

In some variations, the memory may include a database (not shown) andmay be, for example, a random access memory (RAM), a memory buffer, ahard drive, an erasable programmable read-only memory (EPROM), anelectrically erasable read-only memory (EEPROM), a read-only memory(ROM), Flash memory, and the like. The memory may store instructions tocause the processor to execute modules, processes, and/or functionsassociated with the communication device, such as signal processing,infection prediction, turbidity estimation, particle estimation, flowdetection, bubble detection, patient monitoring device control, and/orcommunication. Some variations described herein relate to a computerstorage product with a non-transitory computer-readable medium (also maybe referred to as a non-transitory processor-readable medium) havinginstructions or computer code thereon for performing variouscomputer-implemented operations. The computer-readable medium (orprocessor-readable medium) is non-transitory in the sense that it doesnot include transitory propagating signals per se (e.g., a propagatingelectromagnetic wave carrying information on a transmission medium suchas space or a cable). The media and computer code (also may be referredto as code or algorithm) may be those designed and constructed for thespecific purpose or purposes.

Examples of non-transitory computer-readable media include, but are notlimited to, magnetic storage media such as hard disks, floppy disks, andmagnetic tape; optical storage media such as Compact Disc/Digital VideoDiscs (CD/DVDs); Compact Disc-Read Only Memories (CD-ROMs), andholographic devices; magneto-optical storage media such as opticaldisks; solid state storage devices such as a solid state drive (SSD) anda solid state hybrid drive (SSHD); carrier wave signal processingmodules; and hardware devices that are specially configured to store andexecute program code, such as Application-Specific Integrated Circuits(ASICs), Programmable Logic Devices (PLDs), Read-Only Memory (ROM), andRandom-Access Memory (RAM) devices. Other variations described hereinrelate to a computer program product, which may include, for example,the instructions and/or computer code disclosed herein.

The systems, devices, and/or methods described herein may be performedby software (executed on hardware), hardware, or a combination thereof.Hardware modules may include, for example, a general-purpose processor(or microprocessor or microcontroller), a field programmable gate array(FPGA), and/or an application specific integrated circuit (ASIC).Software modules (executed on hardware) may be expressed in a variety ofsoftware languages (e.g., computer code), including C, C++, Java®,Python, Ruby, Visual Basic®, and/or other object-oriented, procedural,or other programming language and development tools. Examples ofcomputer code include, but are not limited to, micro-code ormicro-instructions, machine instructions, such as produced by acompiler, code used to produce a web service, and files containinghigher-level instructions that are executed by a computer using aninterpreter. Additional examples of computer code include, but are notlimited to, control signals, encrypted code, and compressed code.

In some variations, the patient monitoring device may further comprise acommunication device configured to permit a patient and/or to controlone or more of the devices of the system. The communication device maycomprise a network interface configured to connect the computing deviceto another system (e.g., Internet, remote server, database) by wired orwireless connection. In some variations, the patient monitoring devicemay be in communication with other devices via one or more wired and/orwireless networks. In some variations, the network interface maycomprise a radiofrequency receiver, transmitter, and/or optical (e.g.,infrared) receiver and transmitter configured to communicate with one ormore devices and/or networks. The network interface may communicate bywires and/or wirelessly.

The network interface may comprise RF circuitry configured to receiveand send RF signals. The RF circuitry may convert electrical signalsto/from electromagnetic signals and communicate with communicationsnetworks and other communications devices via the electromagneticsignals. The RF circuitry may comprise well-known circuitry forperforming these functions, including but not limited to an antennasystem, an RF transceiver, one or more amplifiers, a tuner, one or moreoscillators, a digital signal processor, a CODEC chipset, a subscriberidentity module (SIM) card, memory, and so forth.

Wireless communication through any of the computing and measurementdevices may use any of plurality of communication standards, protocolsand technologies, including but not limited to, Global System for MobileCommunications (GSM), Enhanced Data GSM Environment (EDGE), high-speeddownlink packet access (HSDPA), high-speed uplink packet access (HSUPA),Evolution, Data-Only (EV-DO), HSPA, HSPA+, Dual-Cell HSPA (DC-HSPDA),long term evolution (LTE), near field communication (NFC), wideband codedivision multiple access (W-CDMA), code division multiple access (CDMA),time division multiple access (TDMA), Bluetooth, Wireless Fidelity(WiFi) (e.g., IEEE 802.11a, IEEE 802.11b, IEEE 802.11g, IEEE 802.11n,and the like), voice over Internet Protocol (VoIP), Wi-MAX, a protocolfor e-mail (e.g., Internet message access protocol (IMAP) and/or postoffice protocol (POP)), instant messaging (e.g., extensible messagingand presence protocol (XMPP), Session Initiation Protocol for InstantMessaging and Presence Leveraging Extensions (SIMPLE), Instant Messagingand Presence Service (IMPS)), and/or Short Message Service (SMS), or anyother suitable communication protocol. In some variations, the devicesherein may directly communicate with each other without transmittingdata through a network (e.g., through NFC, Bluetooth, WiFi, RFID, andthe like).

Power Source

In some variations, the patient monitoring device may receive power froman external power source (e.g., wall outlet, generator). The patientmonitoring device may receive power via a wired connection, and/or awireless connection (e.g., induction, RF coupling, etc.). Additionallyor alternatively, the patient monitoring device may comprise a portablepower source such as a battery. As described in more detail herein, thepatient monitoring device may comprise one or more power algorithmsconfigured to conserve energy and increase a lifespan of the patientmonitoring device.

Drain Line Extension

The fluid conduits described here may be configured to allow patientfluid to flow through an optical measurement portion for patientinfection prediction and/or other characterizations of the patientfluid. In some variations, the fluid conduit may be configured to extenda length of a drain line. Furthermore, the fluid conduit may be adisposable component. In some variations, a fluid conduit may be fluidlycoupled to an optically transparent vessel configured for illuminationand optical measurement. The vessel may comprise one or more alignmentfeatures configured to align the vessel (e.g., in rotation and/or depth)to a patient monitoring device described herein.

FIG. 16A is a perspective view of a drain line extension (1600) and FIG.16B is an exploded perspective view of the drain line extension (1600).In some variations, the drain line extension (1600) may comprise one ormore of a vessel (1610), cap (1620), fluid conduit (1630), firstconnector (1640), second connector (1642), first vent cap (1650), secondvent cap (1652), vessel extension (1660), shut-off clamp (1670), andpackaging holder (1680) (e.g., tape, strip, band). An inlet of thevessel (1610) may be coupled to the vent extension (1660) and an outletof the vessel (1610) may be coupled to the cap (1620). The ventextension (1660) may have a length sufficient such that the firstconnector (1640) is external to a housing of a patient monitoring devicewhen the drain line extension (1600) is coupled to a patient monitoringdevice. An inlet of the vent extension (1660) may be coupled to thefirst connector (1640) (e.g., male dialysis connector). The first ventcap (1650) may couple to the first connector (1640). An outlet of thecap (1620) may couple to an inlet of the fluid conduit (1630). An outletof the fluid conduit (1630) may couple to the second connector (1642)(e.g., female dialysis connector), and a second vent cap (1652). In somevariations, at least a portion of the fluid conduit (1630), vesselextension (1660) and/or other vent caps, connectors, etc. may benon-transparent to further block or otherwise control entry of ambientlight into the drain line extension.

FIG. 17A is a perspective view of a drain line extension (1700) and FIG.17B is an exploded perspective view of the drain line extension (1700).In some variations, the drain line extension (1700) may comprise one ormore of a vessel (1710), cap (1720), fluid conduit (1730), connector(1740) (e.g., bushing), first vent cap (1750), second vent cap (1752),shut-off clamp (1760), and packaging holder (1770) (e.g., tape). Aninlet of the vessel (1710) may be coupled to the first vent cap (1750)(e.g., spike vent cap) and an outlet of the vessel (1710) may be coupledto the cap (1720). An outlet of the cap (1720) may couple to an inlet ofthe fluid conduit (1730). An outlet of the fluid conduit (1730) maycouple to the connector (1740) and a second vent cap (1752). In somevariations, at least a portion of the fluid conduit (1730) and/or othervent caps, connectors, etc. may be non-transparent to further block orotherwise control entry of ambient light into the drain line extension.

Although FIGS. 17A and 17B depict a drain line extension including anoptically transparent vessel configured for illumination and opticalmeasurement, it should be understood that in other variations anoptically transparent vessel may additionally or alternatively bearranged along any portion of a fluid conduit in fluidic communicationwith a drainage output of a cycler. For example, in some variations, adrain line that is part of a base tubing set (rather than a drain lineextension) may include an optically transparent vessel or opticallytransparent measurement portion. For example, FIG. 17C is a perspectiveview of an exemplary variation of a cycler drain line (1701) assembledwith a vessel (1711). The cycler drain line (1701) may comprise a firstportion (1734) (e.g., inlet) and a second portion (1732) (e.g., outlet).For example, a vessel (1711) comprising an optically transparentmeasurement portion as described herein may be assembled in-line withthe drain line (e.g., tubing set) (1701). In some variations, the vessel(1711) may be configured to attach to the drain line (1701) using asolvent bond and/or adhesive as described herein. The integrated drainline (1701) depicted in FIG. 17C may, for example, reduce the number ofassembly steps in CCPD treatment and therefore may increase patientcompliance and sterility.

In some variations, a fluid vessel (e.g., optically transparentmeasurement portion) may be disposed within one or more portions of adrain line or drain line extension (e.g., proximal, distal, andin-between). In some variations, an optically transparent measurementportion may be disposed within an end portion (e.g., proximal portion,distal portion) of a drain line. For example, a CAPD system may comprisea drain line coupled between a Y-connector and a drainage vessel where aproximal portion of the drain line may comprise an optically transparentmeasurement portion adjacent to (e.g., downstream of) the Y-connector.As another example, a proximal end of an in-dwelling catheter maycomprise a fluid vessel as described herein. In a CCPD system, anoptically transparent measurement portion of the in-dwelling cathetermay be coupled adjacent to the drain line of the cycler tubing set. Anoptically transparent measurement portion disposed at an end of a drainline may reduce manufacturing complexity and therefore reduce associatedcosts.

The drain line extensions described herein may be compatible withstandard connectors and/or adapters. The vent caps may be configured toprotect a lumen of the fluid conduit and vessel from contamination. Forexample, a spike vent cap may be configured to protect a packaging ofthe drain line extension from being punctured by the sharp tip of thevessel. One or more of the vent caps may additionally or alternativelyinclude anti-contamination features such as tortuous channels to helpprevent passage of contaminants into the drain line fluid conduit. Insome variations, one or more outer surfaces of the drain line extension,except for an optical measurement region of the vessel, may be texturedso as to prevent sticking and/or reduce ambient light leakage into thevessel. In some variations, one or more portions of the drain lineextension, except for an optical measurement region of the vessel, maybe non-transparent to reduce ambient light leakage into the vessel. Forexample, the cap may be opaque and the fluid conduit may be translucent.The inlet and outlet portions of the vessel may be non-transparent aswell.

The drain line extension may further include a measurement vessel, whichmay define a volume receiving patient fluid for measurement by thepatient monitoring device. Conventional cuvettes used for fluid analysisgenerally have precise dimensions and must meet strict manufacturingtolerances that do not allow for injection molding and similarcost-effective techniques. However, in contrast, the vessels describedherein may comprise a number of structural features which may be formedutilizing high yield, low-cost manufacturing techniques such asinjection molding and solvent bonding, while enabling high qualityoptical measurements, as further described below.

FIGS. 18A-18I are various views of a vessel (1800) for use in a fluidconduit comprising an inlet (1810) (e.g., spike), outlet (1830), and anoptically transparent measurement portion (1820) between the inlet(1820) and outlet (1830). The measurement portion (1820) may comprise aninternal volume configured to receive fluid such as patient fluid.During use of the vessel (1800), patient fluid may pass into themeasurement portion (1820) through the inlet (1810) and pass out of themeasurement portion (1820) through the outlet (1830). For example, thepatient fluid may be continuously pumped through the vessel (1800)during a measurement period. At least one cap (1870) may be coupled toan outlet (1830) and/or inlet of the vessel. A fluid conduit (1880) maybe coupled to an outlet of the cap (1870). A drain line or other tubingmay be coupled to the inlet (1820).

In some variations, the vessel (1800) may be comprise one or moreoptical features configured to aid optical measurement of patient fluidthrough the vessel (1800). The measurement portion (1820) may compriseat least two substantially planar surfaces that may be orthogonal toeach other or opposite to each other. Such planar or flat surfaces maybe advantageous for the devices and methods described herein, becauseless light bending is incurred by flat surfaces (compared toconventional, round-surfaced cuvettes). As shown in FIG. 18G, themeasurement portion (1820) may comprise a square cross-section. Thesubstantially planar surfaces and square cross-section may reducerefraction relative to a cylindrical conduit and may improve theconsistency and quality of optical measurement through the vessel(1800). The square cross-section may further aid alignment of the vessel(1800) with an optical sensor arrangement of a patient monitoringdevice.

In some variations, the internal volume of the measurement portion(1820) may comprise one or more bubble mitigation features that mayreduce the generation and presence of bubbles within the vessel (1800),and thus increase a signal-to-noise ratio of optical measurements usingthe vessel (1800). For example, the internal volume may comprise bubblemitigation features such as radiused corners (1860) and a taper (1822).Radiused corners may reduce the number of sharp transitions and edgeswhere bubbles may form and accumulate (e.g., during an initial fluidfill, during continuous flow, etc.).

In some variations, the vessel (1800) may comprise one or more ambientlight reduction features to reduce ambient light leakage into themeasurement portion (1820) of the vessel. For example, one or more ofthe inlet (1810) and outlet (1830) may include a non-transparent (e.g.,opaque, translucent) material and/or coating. One or more of the inlet(1810) and outlet (1830) may comprise texturing to provide a gripinterface for a patient and/or form a light seal. Furthermore, anon-transparent connector may be coupleable to the inlet (1810) and/orthe outlet (1830).

In some variations, the vessel (1800) may comprise one or more alignmentfeatures configured to aid engagement and positioning of the vessel(1800) relative to an optical sensor arrangement of a patient monitoringdevice. For example, the vessel (1800) may comprise a depth alignmentfeature (1840) and/or a rotational alignment feature (1850). In somevariations, the depth alignment feature (1840) may be disposed around aperimeter of the vessel (1840). The depth alignment feature (1840) mayengage with a shoulder or other mating or interfering feature of theholder in the patient monitoring device (e.g., shoulders (1253) of thepatient monitoring device (1200) shown in FIG. 12A). The rotationalalignment feature (1850) may engage with a slot or recess of the holderin the patient monitoring device (e.g., engagement feature (1012) of theholder shown in FIG. 10A). In some variations, the rotational alignmentfeature (1850) may be formed so to not overlie regions of themeasurement portion (1820) that will be aligned with the illuminationsources and optical sensors in the patient monitoring device when thevessel is placed in the patient monitoring device. Accordingly, in thesevariations, the placement of the rotational alignment feature (1850) isselected as to avoid interfering with optical measurements. For example,as shown in FIGS. 18C-18F, the rotational alignment feature (1850) maybe arranged over a corner of the measurement portion (1820) rather thanover one of the planar surfaces. The depth alignment feature (1840)and/or rotational alignment feature (1850) may comprise protrusions.

In some variations, the vessel (1800) may comprise one or more featuresconfigured to aid manufacturing of the vessel (1800). In somevariations, at least a portion of the measurement portion (1820) may betapered. For example, the measurement portion (1820) may comprise adraft of between about 0.5 degrees and 2 degrees. Moreover, injectionmolded parting lines may be located above and below the opticalmeasurement portion (e.g., along the depth alignment feature). In somevariations, the vessel (1800) may be coupled to a cap (1870) (such asthat described below) by solvent bonding. Solvent bonding may be acost-effective and efficient manufacturing technique. For example, thesolvent may comprise a cyclohexanone and/or methyl ethyl ketone.

In some variations, the vessel (1800) may be composed of a materialhaving good optical clarity and high transmission properties of desiredwavelengths of light. For example, the vessel may comprise one or moreof copolyester, acrylonitrile butadiene styrene, polycarbonate, acrylic,cyclic olefin copolymers, cyclic olefin polymers, polyester,polystyrene, ultem, polyethylene glycol-coated silicone, zwitterioniccoated polyurethane, polyethylene oxide-coated polyvinyl chloride, andpolyamphiphilic silicone. For example, the vessel (1800) may be composedof VLD-100 Acrylic, Cyro H15-011 acrylic, Acritherm HS Acrylic HS3125,Acrylic V825, Acritherm HS3, Cyclo-Olefin Polymer Zeonex E48R,Cyclo-Olefin Polymer Zeonex 1020R, Cyclo-Olefin Polymer 1060R,Cyclo-Olefin Polymer TPX RT-18, COC Topas, Polycarbonate LExan 1130-112,Lexan HSP6-1125, Polyester OKP4, Dow 685D Polystyrene, and Ultem1010-1000.

In some variations, a cap may be coupled to an end (e.g., inlet, outlet)of a vessel and may function as a connector for a fluid conduit. Forexample, the cap may provide a transition between the vesselcross-section and a cross-section of the rest of the fluidic conduit(e.g., from a square cross-section of the vessel to a circularcross-section of the fluidic conduit). FIGS. 19A-19D are various viewsof a cap (1900) for a vessel comprising an outlet (1910), inlet (1920),and grip (1930). In some variations, the cap (1900) may comprise one ormore ambient light reduction features to reduce ambient lightpropagation from tubing of the fluid conduit into the vessel. Forexample, the cap (1900) may include a non-transparent material and/orcoating (e.g., opaque, translucent). Furthermore, an outer surface ofthe grip (1930) may comprise texturing to provide a grip interface for apatient and/or form an ambient light seal. For example, the grip (1930)on the cap (with the cap coupled to the vessel) may allow the patient tohandle the vessel without touching and contaminating the opticallysensitive transparent sidewalls. In some variations, the grip mayinclude one or more recesses that are configured to receive a finger,though in other variations the grip may additionally or alternativelyinclude outwardly projecting texturing such as ribs, etc.

In some variations, the cap (1900) may be coupled to the vessel via aninterference fit. In some variations, the cap (1900) may have avessel-interfacing surface that is configured to fit over an end (outletor inlet) of the vessel, and is undersized relative to the end of thevessel to promote an interference fit. Alternatively, in othervariations, the cap (1900) may have a vessel-interfacing surface that isconfigured to fit within an end (outlet or inlet) of the vessel, and isoversized relative to the end of the vessel to promote an interferencefit. Furthermore, in these variations the cap (1900) may include amaterial that is less rigid (e.g., semi-rigid) than the vessel tofurther enable the interference fit between the cap (1900) and vessel.Additionally or alternatively, the cap may be coupled to the vessel viasolvent bonding. In some variations, the cap (1900) may comprise asemi-rigid material such as PVC (e.g. shore hardness 90A), the vesselmay comprise a rigid material such as Copolyester (e.g., Tritan MX731),and the cap (1900) may be further solvent bonded to the vessel withsolvent-cyclohexanone and/or methyl ethyl ketone.

As shown in FIGS. 19C and 19D, in some variations, an internal volume ofthe cap (1900) may comprise one or more interfaces (1960, 1962)configured to provide an internal stop for engagement to an outlet of avessel or fluid conduit. For example, the cap (1900) may include avessel-interfacing stop (1960) configured to engage or mate with an endof the vessel, and/or a conduit-interfacing stop (1962) configured toengage or mate with an end of a fluidic conduit. In some variations, thecap may be coupled to the end of a fluidic conduit with solvent bonding,similar to that described above.

In some variations, the internal volume may further comprise one or morebubble mitigation features similar to that described above for thevessel, such as radiused corners (1940) and/or tapered transitions inshape.

Patient Monitoring Methods

Also described here are methods for monitoring a patient fluid using thesystems and devices described herein. For example, methods may compriseone or more of predicting infection of a patient, estimating particleconcentration of a fluid, estimating fluid flow, and bubble detection.These methods may be useful for monitoring peritoneal dialysis patientsthat use in-dwelling catheters that are susceptible to infectioncomplications. It should be appreciated that any of systems and devicesdescribed herein may be used in the methods described herein.

Infection Prediction

Generally, the methods for predicting infection may be based on opticalmeasurements of patient fluid. For example, optical scatter and/orobscuration of the patient fluid may be measured through an opticallytransparent vessel. These optical measurements may be used to estimateturbidity values of the patient fluid. Furthermore, specific particleconcentrations may be estimated based on light absorption patternsacross specific wavelengths and the resultant variations in lightscatter sensor outputs. An infection score may be generated based on theestimated optical properties (e.g., turbidity) and/or the change of theoptical properties over time. A prediction that a patient is infectedmay be based on one or more of the infection score and a set ofpredetermined criteria.

As described above, generally, infection may be correlated withconcentration of one or more particle types, such as leukocytes, in thepatient fluid. Concentration of leukocytes and/or other particle typesmay be estimated or measured based on a turbidity of the patient fluid,as estimated or measured using methods and devices such as thosedescribed herein.

In some variations, a method of predicting infection may includeilluminating a patient fluid in a fluid conduit from a plurality ofillumination directions. For example, the illumination directions may begenerally orthogonal to each other, or approximately 180 degrees offsetfrom each other.

In some variations, illumination output from a single illuminationsource enables a scatter angle light intensity measurement (e.g., 90degrees) and an absorption/obscuration/attenuation angle light intensitymeasurement (e.g., 180 degrees). For example, in FIG. 14A, the firstoptical sensor (1420) may be configured to measure 180 degree scatterangle (e.g., attenuation) light intensity measurements of patient fluid(T₁) based on illumination output from the first illumination lightsource (1410). The first optical sensor (1420) may further measure 90degree scatter angle light intensity measurements of patient fluid (N₂)based on illumination output from the second illumination light source(1412). Similarly, the second optical sensor (1422) may be configured tosubsequently measure 180 degree scatter angle light intensitymeasurements of patient fluid (T₂) based on illumination output from thesecond illumination light source (1412). The second optical sensor(1422) may further measure 90 degree scatter angle light intensitymeasurements of patient fluid (N₁) based on illumination output from thefirst illumination light source (1410). The light intensity measurements(T_(n), N_(n)) may be measured separately (e.g., sequentially) such thatan optical sensor measures light intensity from a single illuminationsource and not a plurality of illumination sources at the same time.

In some variations, the first illumination source (1410) and the secondillumination source (1412) may illuminate the patient fluid in a firstplane such that a first illumination direction of the first illuminationsource (1410) and a second illumination direction of the secondillumination source (1412) are substantially coplanar. In somevariations, the patient fluid may be illuminated through a plurality ofparallel illumination planes (e.g., first plane, second plane, thirdplane) substantially orthogonal to a fluid conduit.

In some variations, each illumination source in an illumination plane(e.g., first plane, second plane, third plane) may illuminate patientfluid at a same wavelength such that the illumination sources in theillumination plane output redundant wavelengths. A plurality ofillumination sources illuminating the patient fluid at the samewavelength may improve optical sensor measurements by canceling outerroneous signals, for example.

In some variations, sensor measurement error detection may be performedto exclude unreliable light intensity measurements that may result fromsources of error such as damaged, malfunctioning, or dirty opticalcomponents (e.g., illumination source, optical sensor) in the opticalsystem. In some variations, paired light intensity measurements may alsobe used to validate the light intensity measurements. For example, lightintensity measurements of patient fluid N₁ and N₂ may be used tocalculate a percentage difference

$\left( {{e.g.},{\frac{\left( {{N2} - {N1}} \right)}{N1} \times 100}} \right).$

In some variations, both of the light intensity measurements may beinvalidated (e.g., not used) if the percentage difference exceeds apredetermined threshold (e.g., 10%). In other variations, the higherlight intensity measurement may be invalidated (e.g., not used) if thepercentage difference exceeds a predetermined threshold (e.g., 10%), andonly the lower value measurement would be used.

In some variations, an illumination source such as an LED may emit lightbased on pulse width modulation (PWM). In some variations, a firstillumination source using PWM may emit multiple light pulses (pulse “ON”phase) during which a first optical sensor may synchronously measure thelight intensity during the pulse ON phase, followed by measurementsusing a second optical sensor. The first illumination source may turnOFF and a second illumination source using PWM may emit multiple lightpulses (pulse “ON” phase), during which the second optical sensor maysynchronously measure the output during the pulse ON phase, followed bymeasurements using the first optical sensor. During each PWM ONsequence, a single measurement or a plurality of measurements may betaken by the optical sensors. Multiple measurements allow forstatistical processing of the measurements, such as deriving themeasurement's average, median, standard deviation, minimum, maximum, ormore complex statistical modeling such as outlier analysis and removal.During the PWM ON sequence, the optical sensors may be configured to adda delay before measuring within each pulse ON phase to account for thewarm-up stabilization time of the illumination source in order toprovide more accurate optical measurements. The delay for warm-upstabilization may comprise a portion of a single pulse or multiplepulses.

Generally, the measured optical characteristics may be used to estimateturbidity of the patient fluid, which may be correlated to particle(e.g., leukocyte) concentration in order to provide an indication ofinfection state (e.g., based on empirical correlations). The 180 degreescatter angle light intensity measurements (T₁, T₂) are more sensitiveto changes in illumination intensity than for 90 degree scatter anglelight intensity measurements (N₁, N₂). In some variations, the firstillumination light source (1410) may illuminate the patient fluid andthe first optical sensor (1420) may measure T₁ and the second opticalsensor (1422) may measure N₁. Then, the second illumination light source(1412) may illuminate the patient fluid and the first optical sensor(1420) may measure N₂ and the second optical sensor (1422) may measureT₂. The time period between sequential optical measurements using thefirst and second illumination sources should be minimized to ensuremeasurement of the same portion of patient fluid. Based on thesemeasurements, the turbidity of the patient fluid may be estimated basedon the equations Turbidity₁ and Turbidity₂, below:

Turbidity₁=√{square root over ((N ₁ *N ₂)/(T ₁ *T ₂))}

Turbidity₂=√{square root over ((N ₁ *N ₂))}

The Turbidity₁ equation may provide high accuracy and the Turbidity₂equation may be robust against changes in light intensity due to thelight sources, and/or due to variances in the vessel (e.g.,manufacturing variations). In some variations, the turbidity equationused to estimate a turbidity of the patient fluid may be selected basedon a measured light intensity variation between the optical sensors. Forexample, if the measured T₁ and T₂ are within a predetermined range ofeach other (e.g., 75%, 80%, 85%, 90%, 95%, 98%, etc.), then turbiditymay be estimated using the Turbidity₁ equation. Otherwise, turbidity maybe estimated using the Turbidity₂ equation. In some variations,turbidity may be estimated using both equations and some combination ofthe estimated turbidities may be used. For example, the estimatedturbidities may be averaged and/or weighted. Furthermore, the estimatedturbidities may be sampled over a predetermined time period with the setof samples being averaged and/or weighted. For example, a singleturbidity value used for infection prediction may be generated for eachdrain cycle based on an averaging of a plurality of estimatedturbidities during the drain cycle. In some variations, a samplingfrequency of the patient fluid may be increased based on a predictedpositive infection state.

In some variations, the measured optical characteristics of the patientfluid illuminated from a plurality of illumination directions may beused to calibrate the patient monitoring device. For example, asignificant difference between the measured T₁ and T₂ may indicate thatat least one of the illumination sources may be failing and should bereplaced. In response, one or more of the patient, provider, andmanufacturer may be notified that the patient monitoring device requiresservicing and/or replacement. For example, the patient may be notifiedto “Call Provider” or “Replace Device” by the patient monitoring device.In some of these variations, the patient monitoring device may ceasepatient monitoring functions until calibration and/or servicing isperformed.

In some variations, illumination output from a single illuminationsource enables a plurality of scatter angle light intensity measurements(e.g., 90 degrees). Although the optical sensors in this configurationdo not provide 180 degree scatter angle light intensity measurements,they are configured to capture side scatter illumination from differentillumination sources. For example, in FIG. 14B, the first optical sensor(1420) may be configured to separately measure 90 degree scatter anglelight intensity measurements (N_(1,1) and N_(2,1)) based on respectiveillumination output from the first illumination light source (1410) andthe second illumination source (1412). Similarly, the second opticalsensor (1422) may be configured to measure 90 degree scatter angle lightintensity measurements (N_(1,2) and N_(2,2)) based on respectiveillumination output from the first illumination light source (1410) andthe second illumination light source (1412).

Turbidity₃=√{square root over ((N _(1,2) *N _(2,2))/(N _(1,1) *N_(2,1)))}

The Turbidity₃ equation may be robust against changes in light intensityrelative to the Turbidity₁ equation.

In some variations, the turbidity (as determined by one or more of theabove-described turbidity equations) may be correlated to an infectionstate (e.g., based on empirical correlations), which may be quantifiedwith an infection score. The infection score may, for example, beexpressed in terms of nephelometric turbidity units (NTU). In somevariations, the estimated turbidity may be scaled (e.g., normalized) toan infection score scale, such as between 0-100. In another variation,an infection score may be based on the rate of change of turbiditymeasured of successive samples over a predetermined time period (e.g.,24 hours).

Additionally or alternatively, as further described below, any one ormore of the above turbidity equations may be used to determine one ormore other patient fluid characteristics, such as particle compositionestimation, fluid flow estimation (e.g., detecting whether the cycler isON or OFF), detecting bubbles in the patient fluid, etc.

Ambient Light Subtraction

Ambient light leakage or propagation through one or more of the housingof the patient monitoring device, fluid conduit, and the vessel mayalter optical measurements due to factors such as manufacturingtolerances, wear, and environmental conditions. In some variations, anoptical sensor may be calibrated at predetermined intervals tocompensate for ambient light leakage. Accordingly, ambient light (e.g.,not generated by an illumination source) may be removed from themeasured signals to improve the estimated turbidity, infectionprediction, and other analysis performed on the measured signals.

In some variations, ambient light noise may be measured and removed fromsubsequent optical measurements and signal processing. For example, abaseline optical measurement corresponding to ambient light levels maybe performed. This baseline may be subtracted from the subsequentoptical measurements and may, for example, improve the estimatedturbidity and infection prediction. In some variations, the baselineoptical measurement may be performed when the empty fluid conduit andvessel are initially attached and enclosed within a patient monitoringdevice and when the illumination sources are turned OFF. Any signalmeasured by the optical sensors during this baseline measurement (“dark”signal) may be attributed to ambient light leakage and/or electricalnoise. Subsequent optical measurements may be calibrated against thisbaseline measurement where the baseline measurement is subtracted fromeach subsequent optical measurement (“light” signal). In other words,the “true” measurement specifically attributable to characteristics ofthe patient fluid may be determined as the difference between the“light” signal and the “dark” signal. In another variation, an opticalmeasurement of the patient fluid may include a baseline measurement. Forexample, the following sequence may be used: While first and secondillumination sources are OFF, a dark signal is be measured at the firstand second optical sensors. The first illumination source is turned ONand light intensity is measured at the first and second optical sensors.The first illumination source is turned OFF and a dark signal ismeasured at the first and second optical sensors. The secondillumination source is turned ON and light intensity is measured at thefirst and second optical sensors. This sequence may be repeated at apredetermined interval (e.g., every optical measurement of the patientfluid). In some variations, an optical sensor disposed on an externalsurface of a housing of a patient monitoring device may additionally oralternatively be used to generate or contribute to the baselinemeasurement.

In some variations, the baseline optical measurement may be performed atany time when the illumination sources are turned OFF and the patientfluid is static or flowing through the vessel. For example, such acalibration may be performed at the beginning of every cycle with the PDmachine, or every time a door of the housing is closed. If at any pointthe baseline optical measurement exceeds a predetermined threshold, oneor more of the patient, provider, and manufacturer may be notified toservice and/or replace the patient monitoring device and/or fluidconduit as it may indicate calibration or device failure. Additionallyor alternatively, the patient may be instructed to reduce the intensityof ambient light sources in the surrounding environment of the patientmonitoring device.

In some variations, a baseline optical measurement may be performed whenan empty vessel is first placed into the patient monitoring device. Inother variations, a baseline optical measurement may be performed when acycler is first set up and a cleaning fluid is primed through thedrainage line. In some variations, a baseline optical measurement may beused to calibrate the patient monitoring device prior to measuring thepatient effluent.

Particle Composition Estimation

In some variations, the particle composition of a patient fluid may beestimated based on measured optical characteristics of the patientfluid. For example, the type and/or concentration of particles (e.g.,erythrocytes, leukocytes, triglycerides, protein, fibrin, etc.) in thepatient fluid may be estimated based on optical measurements of particlesettling characteristics of static patient fluid and/or opticalmeasurements at a predetermined set of wavelength ranges.

In some variations, the estimated particle compensation may be used toimprove the accuracy of detection of an infection state of the patient.For example, the characterization of particle composition using methodsdescribed below may be used to distinguish between “true positives” and“false positives” for infection state determination (e.g., falsepositives may be identified and excluded). For example, if the estimatedturbidity calculated using one of the above-described turbidityequations exceeds a predetermined threshold corresponding to infection,but the estimated particle composition of the patient fluid isdetermined to be predominantly erythrocytes, then the prediction ofinfection may be considered a false positive.

Additionally or alternatively, the estimated particle compensation maybe used to characterize the patient fluid and/or a patient status inother manners. For example, a determination that a patient fluidincludes a high concentration of erythrocytes, the estimated turbidityof the patient fluid may be attributed to bleeding rather thanleukocytes, rather than an infection.

Additionally, or alternatively, the particle type and/or concentrationof particles in the patient fluid may be estimated by the changessuccessive sample measurements over time. For example, a patient mayhave five drainage sessions over a period of 24 hours. In the case of aninfection, leukocyte counts may rapidly increase in concentration aspart of a natural immune response. Therefore, measurement of successivesamples may determine a rate of change in optical measurementscharacterized by a unique ramp-up profile of leukocytes corresponding toinfection. In another example, triglyceride infusion may correspond toan acute, single measurement spike. Subsequent optical measurements maybe characterized by a return to a low, normal baseline value. In yetanother example, bleeding typically causes an immediate spike inmeasured fluid turbidity, and quickly reduces as clotting biologicalmechanisms take over.

Particle Settling

In some variations, a composition of a patient fluid may be estimatedbased on measured optical characteristics over time. For example, suchoptical characteristics of effluent dialysate may be measured during aCCPD exchange. In a typical CCPD exchange, there are three operationalstages, including (1) filling the patient with dialysate fluid byfeeding dialysate into a patient-entering line with a pump, (2) allowingthe dialysate fluid to dwell in the patient while the pump is off, and(3) draining, in a drain cycle, effluent dialysate from the patient byfeeding effluent dialysate into a drain line with the pump. The draincycle typically includes several steps, including (3a) flushing priorfluid from the drain line, where the prior fluid may be effluent fluid,clean fluid from a prior priming and/or purging step, and/or someincidental new patient fluid, (3b) pumping new patient fluid into thedrain line, and (3c) ceasing pumping and allowing the new patient fluidto become static in the drain line.

In some variations, one or more optical measurements may be performedduring step (3b), when new patient fluid is being pumped through thedrain line. For example, optical measurements may be performed at thebeginning, middle, and end of this pumping cycle during step (3b), whichmay indicate how homogenous the new patient fluid is. Homogeneity, forexample, may be estimated based on temporal uniformity of estimatedturbidity as described above). Generally, bigger particles and clumps(e.g., fibrin) are likely to appear less homogenous than smallerparticles like leukocytes. Thus, greater measured homogeneity maysuggest a greater concentration of larger particles such as fibrin.

Additionally or alternatively, one or more optical measurements may beperformed during step (3c), when the fluid flow of the new patient fluidceases (e.g., a pump is turned OFF), and the new patient fluid becomesstatic in the drain line. From the point in time when the pump stops(time=0), optical characteristics of the patient fluid may be measuredat predetermined intervals as the patient fluid settles. In somevariations, the patient fluid may be measured at time=30 sec, 1 min, 2min, 5 min, 15 min, 30 min, 60 min, and so on. Turbidity may beestimated using the measured signal data (as described above) at eachpredetermined interval. Particle properties including mass, buoyancy,density, size, shape, and the like affect the consistency and/orvariance of turbidity measurements over time across these time series ofmeasurements. That is, particle types exhibit unique settlingproperties. Accordingly, the type of particles dominant in a patientfluid may be estimated based on the settling characteristics of thepatient fluid. For example, triglyceride content, having lower densitythan bodily cells, may remain suspended for relatively longer periods oftime. Alternately, white blood cells, being larger and of differentshape from red blood cells, may settle relatively faster. For example,FIG. 20 is a graph (2000) of turbidity of a set of exemplary settlingpatient fluids over time. In graph (2000), the difference in measuredturbidity over time (which is a reflection of settling characteristics)of a first patient fluid (2010) and a second patient fluid (2020)suggest the first patient fluid (2010) and second patient fluid (2020)have different particle compositions.

System of Equations

In some variations, particle composition (e.g., particle concentrations)of a patient fluid may be estimated based at least in part on a systemof equations using inputs including a set of optical measurements at aplurality of wavelength ranges. For example, optical characteristics(e.g., attenuation or scatter signal A_(λn)) of a patient fluid measuredat four wavelength ranges (λ₁, λ₂, λ₃, λ₄) enables the particleconcentrations of leukocytes, erythrocytes, protein (e.g., fibrin), andtriglycerides (ϵ_(k), ϵ_(e), ϵ_(p), ϵ_(t)) to be estimated using thebelow system of equations:

A _(λ) ₁ =c _(l)ϵ_(l,λ) ₁ +c _(e)ϵ_(e,λ) ₁ +c _(p)ϵ_(p,λ) ₁ +c_(t)ϵ_(t,λ) ₁

A _(λ) ₂ =c _(l)ϵ_(l,λ) ₂ +c _(e)ϵ_(e,λ) ₂ +c _(p)ϵ_(p,λ) ₂ +c_(t)ϵ_(t,λ) ₂

A _(λ) ₃ =c _(l)ϵ_(l,λ) ₃ +c _(e)ϵ_(e,λ) ₃ +c _(p)ϵ_(p,λ) ₃ +c_(t)ϵ_(t,λ) ₃

A _(λ) ₄ =c _(l)ϵ_(l,λ) ₄ +c _(e)ϵ_(e,λ) ₄ +c _(p)ϵ_(p,λ) ₄ +c_(t)ϵ_(t,λ) ₄

The optical characteristic A_(λn) may be measured at each of a set ofwavelengths λ₁, λ₂, λ₃, and λ₄. Coefficients C_(l), C_(e), C_(p), andC_(t), may be derived empirically through data models. Thus, for anygiven patient (or other) fluid, the system of equations may thus besolved for the particle concentrations (ϵ_(l), ϵ_(e), ϵ_(p), ϵ_(t)).

In some variations, the set of wavelengths comprises a first wavelengthbetween about 400 nm and about 450 nm (e.g., 415 nm), a secondwavelength between about 500 nm and about 550 nm (e.g., 525 nm), a thirdwavelength between about 230 nm and about 290 nm (e.g., 260 nm), and afourth wavelength between about 860 nm and about 890 nm (e.g., 870 nm).In some variations, the patient fluid may be illuminated sequentially atthe four wavelength ranges in any predetermined order. Furthermore,illumination at these wavelengths may be provided by the sameillumination sources as those providing for turbidity measurements asdescribed above, or may be provided at least in part by a distinct andseparate set of illumination sources.

FIGS. 23A-23D illustrates histograms (2300, 2310, 2320, 2330) ofparticle concentration estimation errors of four particle types for aset of patient fluid samples using the above-described system ofequations approach. The particle concentrations were estimated based onthe system of equations with four particles (leukocytes, erythrocytes,protein, triglycerides) measured at corresponding wavelengths (415 nm,525 nm, 575 nm, 870 nm). The estimation errors were calculated bycomparing the predicted particle concentrations against the actualparticle concentrations determined using spectroscopy. As shown in FIGS.23A-23D, the distributions of particle concentration estimation errorsfor the four particles types were generally centered around zero or asimilarly low number, which suggests that the system of equationsapproach may be an accurate and viable way of estimating particlecomposition of a patient fluid.

Machine Learning

Additionally or alternatively, one or more trained machine learningmodels (or deep learning models, etc.) may be used to determine particlecomposition of patient fluid based at least in part on one or moremeasured optical characteristics, such as a light absorption pattern.For example, one or more suitable machine learning models may be trainedon a suitable training data set including known particle concentrations,such that the trained machine learning model(s) may be able to identifya “signature” in the light absorption pattern suggesting a particlecomposition. Such optical characteristics may be measured at a singlepoint in time, or dynamically to generate a time series of data. Itshould be understood also that any of the above-described variations ofdetermining particle composition may be supplemented with suitablemachine learning methods.

Patient Infection Onset and Resolution

In some variations, methods for predicting infection may includetracking a set of infection scores over time. A turbidity of the patientfluid may be estimated based on the measured optical characteristics,and infection scores may be generated based on the estimated turbidity(e.g., expressed in terms of NTU or similar units). In some variations,the estimated turbidity may be scaled to an infection score scale.

In some variations, an infection score (which may be generated for eachPD cycle, or per day, etc.) may be compared to a set of predeterminedinfection onset criteria to predict onset of an infection state. Forexample, a positive infection state may be predicted in response to theinfection score exceeding a predetermined threshold (e.g., over apredetermined number of consecutive positive infection samples) and/orincreasing relative to a patient-specific baseline over time. Forexample, infection may be predicted in response to an infection scoreexceeding a predetermined threshold during each of one or moresuccessive measurement time periods. In contrast, in some variations, anabsence of infection may be predicted when the number of positiveinfection scores is below a predetermined threshold. In some variations,a false positive infection state may be identified when the infectionscore does not exceed the predetermined threshold over one or moresuccessive measurement time periods. For example, a false positive maybe identified if an infection score threshold is not met for threesample measurements in a row.

By tracking an infection score over time instead of relying upon asingle, discrete sample, the sensitivity and specificity of an infectiondiagnosis may be improved by reducing false positives. For example, FIG.21A illustrates infection detection graphs of an infection score plottedover time. An infection score of 100 may correspond to the InternationalSociety for Peritoneal Dialysis (ISPD) threshold for positive patientinfection. The first graph (2100) shows that only one sample amongtwelve sequential samples has an infection score above the ISPDthreshold. However, a single sample that exceeds the ISPD threshold mayrepresent a false positive.

In contrast, in some variations of the methods and systems describedherein, infection onset prediction criteria may comprise a number ofinfection scores above a predetermined threshold. Specifically, an onsetof a positive infection state may be predicted when the number ofconsecutive positive infection scores is above the predeterminedthreshold (e.g., 2 samples). Additionally or alternatively, infectiononset prediction criteria may comprise a sign and/or rate of change ofthe infection scores. For example, the second graph (2110) shows aplurality of samples having an infection score above the ISPD threshold.Furthermore, the samples above the ISPD threshold are sequential andhave a positive slope such that the onset of infection state of thepatient is predicted with high confidence. In some variations, anindication of the predicted infection state may be output to a patientusing, for example, a display of a patient monitoring device and/or aGUI display on a computing device.

Additionally or alternatively, an infection score (which may begenerated for each PD cycle, or per day, etc.) may be tracked to predictresolution of an infection state. For example, FIG. 21B is an infectiondetection graph (2120) of leukocyte concentration of patient fluid (asmeasured with a conventional method (“Leukocytes”) and as estimated withinfection scores as described herein (“Infection Score”)) plotted overtime for a patient receiving antimicrobial treatment. The infectionscore closely tracks the downward trend in measured leukocyte count,which helps indicate that the methods described herein may be used topredict infection resolution of a patient. Specifically, as shown inFIG. 21B, the actual leukocyte count of the patient initially exceedsthe ISPD threshold for peritonitis. Over time, the leukocyte countdecreases due to antimicrobial treatment and is maintained around theISPD threshold of about 100 cells/μL. Similarly, a set of generatedinfection scores initially exceeds a predetermined threshold and thendecreases until reaching an equilibrium state around a predeterminedoptical score threshold. Therefore, the correlation between an infectionscore and leukocyte count suggests that the infection score may be aproxy for leukocyte count.

In some variations, a set of criteria (e.g., threshold, parameters) usedto predict infection may be generated based on one or more machinelearning techniques such a random forest model. In some variations, theset of predetermined criteria may be generated based on multi-targetlinear regression that relates a set of inputs (e.g., 90 degree- and 180degree-offset light intensity measurements at three wavelengths for apredetermined number of samples). to the concentration or leukocytes,erythrocytes, triglycerides, proteins and more. These continuousvariable predictions may be converted to binary outcomes (negativeinfection, positive infection) based on a set infection thresholds.

In some variations, the set of predetermined criteria may be generatedbased on single-target random forest classification that relates a setof inputs to a single binary target. An infection threshold may beinitially defined by a leukocyte concentration of about 100 cells/μLand/or a polymorphonuclear cells family (PMN) neutrophil concentrationof about 50%. Additionally or alternatively, methods and devicesdescribed herein may be used with any data modeling and/or machinelearning algorithm and/or model, including but not limited tomulti-target regression and classification, decision tree models, deepneural network models, Bayesian networks, clustering models, and/orother algorithms and/or models.

Fluid Flow Estimation

In some variations, estimating a fluid flow rate (e.g., flow ON, flowOFF) of patient fluid through a fluid conduit may enable independentdetermination of an operating state (e.g., pumping state) of a cycler,such as to determine when a unique drain cycle has begun and ceased (andinitiate the optical measurement of the fluid). Furthermore, powerconsumption and optical sensor usage of a patient monitoring device maybe optimized based on a flow state of the patient fluid. For example,the optical sensor may measure patient fluid more frequently when thenight cycler is pumping new fluid through a fluid conduit and reduceoptical sensor usage when patient fluid is static in the fluid conduit.This may increase a lifespan of one or more components of the patientmonitoring device such as an illumination source. In some variations,one or more fluid flow estimation methods may be selected based onpredetermined conditions (e.g., power state, schedule, processing load).As another example, knowledge of the fluid flow rate (ON or OFF) may beused to coordinate processes for estimating particle concentrations inthe patient fluid based on particle settling characteristics (when thecycler pump is OFF), as described above.

In some variations, a fluid flow rate of patient fluid may be estimatedbased on one or more optical measurements of the patient fluid using theoptical sensors described herein. For example, one or more 180 degreescatter angle light intensity measurements of the patient fluid may bemeasured when estimating fluid flow rate, as a 180 degree measurementmay have a relatively high signal-to-noise ratio when compared toscatter signals at other angles. In some variations, the patient fluidmay be sampled at a rate of about 50 Hz to reduce aliasing.

A frequency response of the optical measurement(s) may then be generatedand used to estimate the fluid flow rate. For example, a Fast FourierTransform (FFT) may be applied to a set of optical measurements todetermine whether the frequency of the pulse signal in the opticalmeasurement(s) is approximating a known pump frequency of the cycler.For example, conventional cyclers may pump fluid with a flow ON/OFFcycling frequency of between about 0.05 Hz to about 2 Hz. FIGS. 22A and22B are fluid flow graphs (2200, 2202, 2210) of optical sensormeasurements of fluid plotted over. The optical measurements comprisevariable fluid flow rates (ON, OFF) due to cycler pumping. For example,the flow ON intervals are annotated in each of FIGS. 22A and 22B.Independently, a Fast Fourier Transform (FFT) may be applied to the setof optical measurements to determine whether at any measured point(s) intime the frequency of the optical measurement signal (voltage) isbetween about 0.05 Hz and about 0.2 Hz, which can be used to indicatethe occurrence of a flow ON interval. Conversely, the FFT may be used todetermine whether the frequency of the optical measurement signal is notbetween about 0.05 Hz and about 0.2 Hz, which can be used to indicatethe occurrence of a flow OFF interval.

In some variations, a fluid flow rate of patient fluid may be estimatedusing one or more filters. For example, a fluid flow rate may beestimated using one or more low pass filters and/or high pass filters.Fluid flow estimation based on low pass and/or high pass filters mayreduce computational load relative to, for example, FFT based fluid flowestimation algorithms. For example, a low pass filter may comprise afrequency between about 75 Hz and about 90 Hz, and a high pass filtermay comprise a frequency between about 50 Hz and about 70 Hz. Theoptical measurement signal passed through one or more of the filters maybe analyzed to determine a fluid flow ON/OFF state. For example, afiltered signal comprising a predetermined number of pulses (e.g., 3pulses) above a predetermined threshold may correspond to a fluid flowON state.

Thus, in some variations, an ON or OFF fluid flow state may bedetermined based on the estimated fluid flow rate. In some variations,the patient fluid may be illuminated and measured in response todetecting the ON state (such as to estimate turbidity) and illuminationmay be ceased in response to detecting the OFF state (to conserveenergy). This may reduce power consumption and increase a lifespan of anillumination source by reducing unnecessary and/or constant opticalmeasurements.

For example, optical measurements for fluid flow rate estimation may beperformed at predetermined intervals. For example, such opticalmeasurements may be performed for about thirty seconds in a “listening”state. If the flow is off, then a follow-up set of optical measurementsfor fluid flow rate estimation may repeat after another predeterminedrest interval, such as five minutes. However, if flow is ON, thenoptical measurements may be performed for turbidity estimation such asby using methods described above.

As another example, the patient fluid may be measured and fluid flowrate may be estimated at predetermined intervals throughout a draincycle. For example, the predetermined intervals may comprise thebeginning, middle, and end of new fluid pumping through the fluidconduit during a drain cycle. In some cases, the predetermined intervalsmay comprise a set of intervals (e.g., 1 minute, 2 minutes, 3 minutes,4, minutes, 5 minutes, 10 minutes, etc.) when new fluid becomes staticin the fluid conduit. Additionally or alternatively, fluid flow rate maybe estimated using one or more non-optical sensors. For example, anaccelerometer may be configured to measure vibrations of the fluidconduit corresponding to a fluid flow state. As another example, apressure sensor may be configured to measure periodic or intermittentpressure cycling within a fluidic conduit. As another example, amicrophone may be configured to measure audio corresponding to pumpoperation.

In some variations, the system may be configured to distinguish betweena true fluid flow ON state and a “false positive” fluid flow ON state,such as during one or more cycler setup steps. For example, a falsepositive fluid flow ON state may be generated due to a priming step of aCCPD exchange where fluid intermittently flows through a drain line.Because measurement and sensing during such a priming step (or after anyother brief fluid flow not part of a drain cycle) utilizes the deviceunnecessarily, identification of such false positive fluid flow may helpoptimize device resources and/or usage life (e.g., reduce powerconsumption, reduce memory storage use, reduce unnecessary consumptionof optical sensor lifetime, etc.). In some variations, a false positivefluid flow ON state may be identified based on detecting one or more ofa predetermined number of measured pump pulses over a predeterminedduration of fluid flow. Additionally or alternatively, in somevariations, a false positive may be identified when a fluid flow ONstate is not identified over two or more successive time periods. Forexample, a measurement of three pump pulses within a first measurementtime period having a duration of about 30 seconds may correspond to afluid flow ON state. However, a false positive may be identified if apump pulse threshold is not met (e.g., three pulses) within a secondmeasurement time period having a duration of about 30 seconds measuredafter the first time period. In some variations, a predetermined testdelay time period (e.g., 30 seconds) may be applied between the firsttime period and second time period measurements. If pulses are detectedand a false positive fluid flow ON state has not been identified, thesystem may proceed with the assumption that the fluid flow is indeed inthe ON state, and subsequent optical characteristics of the fluid may bemeasured and analyzed as described herein.

In some variations, a measurement time period as described above (e.g.,first measurement time period, second measurement time period) may bebetween about 10 seconds and about 15 minutes, between about 20 secondsand 5 minutes, between about 20 seconds and about 2 minutes, betweenabout 20 seconds and about 1 minute, between about 20 seconds and 40seconds, including all ranges and sub-values in-between. In somevariations, a test delay time period may be between about 10 seconds andabout 15 minutes, between about 20 seconds and 5 minutes, between about20 seconds and about 2 minutes, between about 20 seconds and about 1minute, between about 20 seconds and 40 seconds, including all rangesand sub-values in-between.

Bubble Detection

In some variations, the patient fluid may comprise non-homogenousobjects such as bubbles that add noise to optical measurements andsubsequent fluid analysis. In some variations, bubbles in the fluidconduit may be detected based at least in part on optical measurementsusing the sensors described herein. FIG. 24 is a bubble graph (2300) ofoptical sensor measurements plotted over time. For example, the flow ONintervals and bubbles are annotated in FIG. 24. In some variations, afrequency response of the optical measurement may be used to detectbubbles. For example, a Fast Fourier Transform (FFT) may be applied tothe optical measurement to generate a corresponding frequency responseplot (not shown). Furthermore, a filter (e.g., low pass filter) may beapplied to differentiate bubbles from flow ON/OFF transitions. Patientfluid including any detected bubbles may be excluded from analysis forinfection, etc. In some variations, a patient may be notified of and/orinstructed to remove the bubbles in the fluid conduit.

Other Monitoring Applications

In some variations, methods for predicting an immune response of thepatient may be based at least in part on the measured opticalcharacteristics. For example, an increased leukocyte count may indicatecomorbidities causing a high immune response not limited to infections,such as from cancer. Immune responses due to different sources typicallycorresponds to a unique differential count profile of one or more typesof leukocytes. Infections, for example, have a higher polymorphonuclearcell differential count. The optical characteristics ofpolymorphonuclear cells vary from other types of leukocytes, such aseosinophils and basophils, which have different sizes and/or shapes.Thus, optical profiles for specific leukocyte types may aid in diagnosisof the root cause of elevated leukocyte levels.

In some variations, methods for predicting bleeding of the patient maybe based on the measured optical characteristics. For example, anoverall turbidity of patient fluid measured above a first predeterminedthreshold in combination with an estimated leukocyte count below asecond predetermined threshold may indicate bleeding. The overallturbidity may be measured at a non-cell-specific wavelength (e.g.,800-900 nm) and the estimated leukocyte count may be measured based onoptical measurements taken at a leukocyte-specific wavelength range. Insome variations, one or more of the patient and provider may be notifiedof possible bleeding.

In some variations, methods for predicting a fibrin concentration may bebased on the measured optical characteristics. For example, highvariance optical measurements may indicate large particulate matter(e.g., solids, clumps, chunks) present in the patient fluid. High fibrincontent may increase a risk of clogging of the fluid conduit.

In some variations, methods for predicting an infection onset for anascites drainage patient may be based the measured opticalcharacteristics. Ascites drainage involves either a permanently affixeddevice (e.g., a peritoneal port or catheter or central venous catheter)or temporarily invasive hospital procedures, such as large volumeparacentesis. Catheter leakage or obstruction may be detected by theflow rate or pressure of the drainage compared to a baseline. Forpatients with frequent ascites drainage (e.g., more than once a week), apatient-specific baseline may be developed over about 3 months or afterabout 25 drainage sessions are measured. For patients with less frequentdrainage, such as on a monthly basis, then comparing the characteristicsof the drainage of the patient against a population baseline may be morepractical. For less frequently drained individuals, data could still becollected to establish an individualized baseline. When a patientmonitoring device is attached to a drainage line, an infection may bemonitored via measurement of the patient fluid and comparing this to thebaseline values of the individual patient.

Remote Monitoring and Clinical Workflow

In some variations, a medical care provider may remotely monitorpatients using methods and systems such as those described herein, whichmay enable early detection and treatment of patients (e.g., withantibiotics for infection treatment, other antimicrobial, etc.). Suchearly detection and treatment may in turn help avoid progression ofinfection and/or other conditions, thereby reducing infection-drivenhospitalization. Although the below description refers primarily to atreatment regimen including administration of an antibiotic, it shouldbe understood that similarly such remote monitoring may be performedwith respect to a treatment regimen including administration of anysuitable antimicrobial (e.g., antibiotic, antifungal, antiviral, etc.).

For example, FIG. 27A illustrates a typical timeline for conventionalstandard of care for a patient with peritonitis. Typically, a patientcontacts their medical care provider upon noticing a visibly cloudysample of effluent dialysate (e.g., as suspected as the result of a“newspaper” test in which a written text sample is not easily visiblethrough a volume of effluent dialysate). The point at which effluentdialysate is visibly cloudy is typically 3-5 days after infection hasoriginated, and in response the medical care provider typicallyprescribes a single broad spectrum antibiotic treatment to address theprogressed infection. However, this approach has a limited success rateof about 72%, as about 28% of patients still end up hospitalized as aresult of a failed antibiotic treatment. Furthermore, hospitalizationmortality rate among such hospitalized patients is about 3.5%. Thus, theconventional standard of care not only relies upon patient compliance toactively monitor for visibly cloudiness of their samples, but also stillleads to a significant portion of the patient population experiencingadverse patient outcomes such as hospitalization or even death.

In contrast, remote patient monitoring using methods and systemsdescribed herein may be used to effectively detect infection soon afterinfection origination and permit prompt courses of action to preventprogression of infection and other conditions. For example, asillustrated in FIG. 27B, a medical care provider may receive anotification of a predicted patient infection state (e.g., probabilityof infection) in about 8-12 hours after infection origination. Thepatient is then prompted (or taken) into the clinic for culture samplewithdrawal, and receives antibiotic treatment (e.g., broad spectrumantibiotic), similar to what typically occurs 3-5 days later underconventional standard of care. After the administration of broadspectrum antibiotic, the patient may continue dialyzing at home, andefficacy of the antibiotic may be remotely monitored as described above.In other words, the medical care provider may be able to determineremotely whether the broad spectrum antibiotic was successful intreating the infection. The success rate for the broad spectrumantibiotic generally is greater if administered earlier rather thanlater, so such early detection provided by the methods and systemsdescribed herein helps efficacy of the broad spectrum antibiotic. If thepatient was successfully treated with the broad spectrum antibiotic,then the patient may be classified as healthy (e.g., case is resolved).If the patient's infection appears to continue to progress (e.g.,determined using methods and systems described herein), then resultsfrom the culture sample (e.g., between about 36 hours-48 hours afterinfection origination) may be used by the medical care provider to shifttreatment toward a more targeted or specific antibiotic. At this pointin the clinical workflow, the patient's infection may be combated with aspecific antibiotic sooner after infection origination, compared toconventional standard of care where the first treatment steps weredelayed due to delayed infection detection.

During the administration of a specific antibiotic, the patient mayagain continue dialyzing at home, and efficacy of the antibiotic may becontinued to be remotely monitored as described above. In other words,the patient's medical care provider may continue to monitor thepatient's infection state (e.g., based on the real-time,device-generated infection score) to confirm whether the infectionsubsides. If the infection is bacterial, then the patient's infection isexpected to be resolves given the specificity of the antibiotic (e.g.,around 5 days after infection origination, depending on resilience ofbacteria, etc.). Only fungal infections, which are nonresponsive toantibiotics, are expected to lead to a hospitalization. Thus, remotepatient monitoring using methods and systems described herein may beused to address patient bacterial infections early and effectively,leaving only a small proportion of fungal infection patients (around 3%of cases) requiring more drastic treatments such as hospitalization.

FIG. 28 illustrates a system implemented in a clinical workflow usingmethods and systems described herein. Generally, a system (2800) formonitoring patients (2810) may include a patient monitoring device(2820) that interfaces with the patient (2810) and may be configured tocommunicate in a wireless or wired manner with a network (2830) (e.g.,cloud-based network or other suitable network of computing device), suchthat data received from the patient monitoring device (2820) may beanalyzed remotely (non-locally) from the patient. Multiple patients(2810) may each have their own patient monitoring device (2820) thatcommunicates in this manner. Alternatively, some patients may share apatient monitoring device (2820) (e.g., multiple patients in a singlehousehold), where data from different patients may be distinguishedusing patient identification info or the like. Alternatively, data fromthe patient monitoring device (2820) may be communicated to one or moreintervening computing devices (not shown) which in turn may communicatedata to the network (2830). Furthermore, in some variations, data may beanalyzed locally by one or more processors on the intervening computingdevice(s). Patient data (and/or information derived from themedical-related data) received by the network may be stored, forexample, on one or more servers.

In some variations, patient data (and/or information derived from thepatient data) may be accessible by one or more third party computingdevices. For example, as shown in FIG. 28, such data or information maybe accessible by a third party computer device (e.g., tablet (2840),mobile phone (2842), laptop computer (2844), desktop computer (2846),etc.) that is in communication with the network (2830). It should alsobe understood that any other computing device operated by the patientmay similarly access the information over the network (2830). Forexample, in some variations, a user (e.g., medical care provider,patient, etc.) may access and/or be notified of patient data through aportal or other suitable graphical user interface. The information (anduse thereof) that may be accessible to other computing devices isfurther described below.

FIG. 29 illustrates, in more detail, a state-based clinical workflowusing methods and systems described herein. Patient states and otherpatient information may be tracked through a graphical user interface(GUI) to permit a user such as a medical care provider to manageremotely monitored patients. For example, as shown in FIG. 29, the usermay access a database of patients using a login (2910) (e.g., user IDand password, other suitable authentication schemes, etc.). A list ofaccessible patients (2912) may be provided to the user for selection andviewing of information (e.g., name, contact info, medical history,current medications, predicted infection status, etc.) associated withthose patients. The patients that are accessible to the user may bepersonalized or otherwise limited. For example, a user who is a medicalcare provider (e.g., doctor or clinic administrator) may be limited toaccess a patient list (2912) including only patients under his or hercare. As another example, a user associated with a medical institution(e.g., clinic) may be limited to access a patient list (2912) includingpatients receiving treatment at the medical institution. The patientlist (2912) may be filtered based on factors such as patient personalcharacteristics (e.g., age, sex, duration of PD treatment, frequency ofinfection, etc.) and/or patient states (2920) or other patient statuses(e.g., as described in further detail below). Furthermore, the GUIand/or other communication system may provide notifications and/orenable note-taking relating to patient status.

FIG. 29 also illustrates an exemplary state diagram of multiple patientstates referred to herein as Stage S-0 to Stage S-5. A patient maygenerally progress from Stage S-0 to Stage S-5 as their conditionworsens (e.g., as infection increases).

Stage S-0 corresponds to a healthy patient state (e.g., no infectionpredicted). An infection of the patient may be predicted (e.g., usingthe devices and methods described herein), which moves the patient fromStage S-0 (“HEALTHY STATE”) to Stage S-1 (“CLINIC 1^(ST) CHECK”)relating to a patient state requiring an initial clinic check. In somevariations, the transition (2930) between Stage S-0 to Stage S-1 mayoccur about 8-12 hours after infection origination.

When in Stage S-1, the patient may be brought into the clinic withinabout 12 hours for a culture sample withdrawal. The patient may betested at the clinic for infection. If there is no infection, thenpatient may return to Stage S-0 (2940). If there is an infection, thepatient may receive broad spectrum antibiotic, along with any othersuitable initial treatments. After receiving initial antibiotictreatment, the patient may be moved (2932) to Stage S-2 (“MONITORINGINITIAL A.B. EFFICACY”).

During Stage S-2, the patient may spend a period of time (e.g., 48hours) at home dialyzing and using patient monitoring devices andmethods described herein. A medical care provider may remotely determinewhether the broad spectrum antibiotic was successful at resolving theinfection (e.g., tracking infection score). If the infection becomesresolved (e.g., based on decreasing trend in infection score), then thepatient may return (2942) to Stage S-0. If the infection appears toprogress (e.g., based on increasing trend in infection score), then thepatient may receive a more targeted or specific antibiotic (e.g., aftera 48-hour period). The specific antibiotic may be determined based atleast in part on the culture sample results for the patient. In somevariations, if the culture sample results suggest a fungal infection,the patient may be moved directly to Stage S-4 (described below), suchas at the discretion of the medical care procedure. Otherwise, afterreceiving a specific antibiotic, the patient may be moved (2934) toStage S-3 (“MONITORING TAILORED A.B. EFFICACY”)

During Stage S-3, the patient may be at home dialyzing and using patientmonitoring systems and methods described herein. During this time,similar to Stage S-2, a medical care provider may remotely determinewhether the specific antibiotic was successful at resolving theinfection (e.g., tracking infection score). In many cases, given thespecificity of the antibiotic administered, the patient's infection willbecome resolved (e.g., reflected in decreasing trend in infectionscore). If the infection becomes resolved, then the patient may return(2944) to Stage S-0. If the infection, however, continues to progress(e.g., based on increasing trend in infection score), then the patientmay become hospitalized and be moved (2936) to Stage S-4(“HOSPITALIZATION”). In many cases, only fungal infections may lead topatient hospitalization.

While in Stage S-4, the patient may receive suitable hospital treatment.If the patient's infection becomes resolved (e.g., as determined bymedical care provider(s)), then the patient may return (2046) to StageS-0. If the infection, however, continues to progress (e.g., asdetermined by medical care provider(s)) and catheter removal isdetermined to be necessary, then the patient's catheter may be removedand the patient may be moved (2938) to Stage S-5 (“MOVED TO H.D.”) forhemodialysis. In some variations, the shift to Stage S-5 forhemodialysis treatment may be permanent, and patients in Stage S-5 mightnot return to peritoneal dialysis. For example, patients permanentlyclassified as Stage S-5 may be classified in the patient monitoringsystem as a former patient or the like.

Thus, early identification or prediction of a patient's infection usingpatient monitoring methods and systems described herein, alone or incombination with remote monitoring and clinical workflow as describedabove, may enable early intervention using appropriate treatment, andhelp avoid advanced patient states such as those requiringhospitalization or hemodialysis.

As described above, the remote monitoring may additionally involve aninterface for a user such as medical care provider, to monitor trends inpatient infection score, patient state, etc., and/or otherwise assist inmanaging patient treatment. For example, FIGS. 28-33 depict exemplaryvariations of GUIs for providing patient information and assisting inpatient management.

FIG. 30 depicts an exemplary variation of a GUI (3000) depicting arecord for a patient of interest in Stage S-0 (“HEALTHY STATE”). Therecord may include, for example, patient identification info (3010) suchas code, name, electronic medical record, or the like associated withthe patient of interest. A patient state (here, Stage S-0) may furtherbe identified in a patient status bar (3012), and historical values ofthe patient's infection score may be displayed over time (3020).Overall, the patient in Stage S-0 is in a healthy state and themonitoring system is relatively passive or non-demanding from a user'spoint of view (e.g., care provider perspective) in that the user is notprompted or notified to perform daily monitoring or checks on thehealthy patient of interest.

FIG. 31 depicts an exemplary variation of a GUI (3100) depicting arecord for a patient of interest in Stage S-1 (“CLINIC 1^(st) CHECK”).GUI (3100) includes one or more fields configured to receive one or moreuser inputs (and/or pull from databases) to help manage proceduraland/or administrative tasks associated with a patient during a cliniccheck, such as whether a culture sample has been taken (3110), whetheran initial antibiotic has been administered (3112), and/or what type ofinitial antibiotic was administered (3114), if any. After thisinformation has been provided and stored, the patient may be moved toStage S-2 as described above. Furthermore, like the GUI depicted in FIG.30, GUI (3100) may include historical values of the patient's infectionscore displayed over time (3120).

FIGS. 32A and 32B depict exemplary variations of a GUI (3200, 3200′)depicting a record for a patient of interest in Stage S-2 (“MONITORINGINITIAL A.B. EFFICACY”). GUI (3200) includes one or more fieldsconfigured to receive one or more user inputs to help manage patienttreatment. For example, GUI (3200) may include fields to receive one ormore user inputs (and/or pull from other databases) such as whether theculture sample was positive (3210), the type of pathogen was in theculture sample if so (3212), the type of recommended or prescribedspecific (tailored) antibiotic (3214), white blood cell count (3216),and (PMN%) (3218). The patient may be remotely monitored using systemsand methods described herein in order to assess efficacy of broadspectrum antibiotic treatment, while the patient dialyzes at home.Furthermore, GUI (3200) may include historical values of the patient'sinfection score displayed over time (3220). Here, GUI (3200) in FIG. 32Adisplays a declining trend (3220) of infection score for a patient whohas responded positively to the broad spectrum antibiotic administered.GUI (3200′) in FIG. 32B may be similar to GUI (3200), except that GUI(3200′) depicts patient trend in infection score (3220′) illustratingthat the patient's infection has worsened, thereby causing the patientto move to Stage S-3.

FIGS. 33A and 33B depict exemplary variations of a GUI (3300, 3300′)depicting a record for a patient of interest in Stage S-3 (“MONITORINGTAILORED A.B. EFFICACY”). GUI (3300) includes one or more fieldsconfigured to receive one or more user inputs to help manage patienttreatment. For example, GUI (3300) may include a field to receive one ormore user inputs (and/or pull from other databases) such as whether toescalate the patient to hospitalization (3310). The patient may beremotely monitored using systems and methods described herein in orderto assess efficacy of specific antibiotic treatment, while the patientdialyzes at home. Furthermore, GUI (3300) displays a declining trend(3320) of infection score for a patient who has responded positively tothe specific antibiotic administered. GUI (3300′) may be similar to GUI(3300), except that GUI (3300′) depicts patient trend in infection score(3320′) illustrating that the patient's infection has worsened, therebycausing the patient to move to Stage S-4.

FIG. 34 depicts an exemplary variation of a GUI (3400) depicting arecord for a patient of interest in Stage S-4 (“HOSPITALIZATION”)receiving treatment in the hospital. Various patient characteristicsand/or medical treatment details may be displayed in GUI (3400), such asa record of whether the patient's catheter has been removed in thecourse of hospital treatment (3410). If, upon completion of hospitaltreatment the input in response to this question is “No,” then thepatient may be moved to Stage S-0. If the input in response to thisquestion is “Yes”, then the patient may be moved to Stage S-5.

FIG. 35 depicts an exemplary variation of a GUI (3500) depicting arecord for a patient of interest in Stage S-5 (“MOVED TO H.D.”). In thisexample, the GUI (3500) indicates this disposition of this patient ofinterest in Stage S-5 as permanently moved to hemodialysis after havingtheir catheter removed. In some variations, GUI (3500) may remain as apermanent record of the status of the patient of interest even thoughthe patient of interest is no longer being remotely monitored forperitonitis. In other variations, the record for this patient ofinterest may be deleted after a predetermined period of time (e.g., 6months, 1 year, 5 years, etc.) and/or as part of database cleanup andmaintenance, etc.

Exemplary Embodiments

Embodiment A1. A method of predicting infection of a patient,comprising:

-   -   illuminating a patient fluid in a fluid conduit from a plurality        of illumination directions;    -   measuring an optical characteristic of the illuminated patient        fluid using one or more sensors; and    -   predicting an infection state of the patient based at least in        part on the measured optical characteristic.

Embodiment A2. The method of claim A1, wherein the plurality ofillumination directions comprises a first illumination direction and asecond illumination direction orthogonal to the first illuminationdirection.

Embodiment A3. The method of claim A2, wherein the predicted infectionstate of the patient is based at least in part on one or more 90-degreescatter angle light intensity measurements from the one or more sensors.

Embodiment A4. The method of claim A3, wherein the predicted infectionstate of the patient is further based at least in part on one or more180-degree attenuation light intensity measurements from the one or moresensors.

Embodiment A5. The method of claim A1, wherein the plurality ofillumination directions comprises a first illumination direction and asecond illumination direction 180 degrees offset from the firstillumination direction.

Embodiment A6. The method of claim A1, wherein illuminating the patientfluid comprises illuminating the patient fluid at a first wavelengthfrom a first illumination direction and at the first wavelength from asecond illumination direction, wherein the first and second illuminationdirections extend along a first plane.

Embodiment A7. The method of claim A6, wherein illuminating the patientfluid comprises illuminating the patient fluid along at least the firstplane and along a second plane substantially parallel to the firstplane.

Embodiment A8. The method of claim A1, wherein illuminating the patientfluid comprises illuminating the patient fluid at a first wavelengthbetween about 800 nm and about 900 nm.

Embodiment A9. The method of claim A8, wherein illuminating the patientfluid comprises illuminating the patient fluid sequentially at aplurality of wavelengths including the first wavelength.

Embodiment A10. The method of claim A9, wherein the plurality ofwavelengths comprises a second wavelength between about 400 nm and about450 nm, and a third wavelength between about 500 nm and about 550 nm

Embodiment A11. The method of claim A10, wherein illuminating thepatient fluid comprises sequentially illuminating the patient fluid atthe third wavelength, the first wavelength, and then the secondwavelength.

Embodiment A12. The method of claim A10, wherein the plurality ofwavelengths comprises a fourth wavelength between about 230 nm and about290 nm.

Embodiment A13. The method of claim A1, wherein the opticalcharacteristic comprises one or more of optical scatter and attenuationdetection angles.

Embodiment 14. The method of claim A1, wherein predicting the infectionstate comprises generating an infection score.

Embodiment A15. The method of claim A14, further comprising estimatingturbidity of the patient fluid based at least in part on the measuredoptical characteristic, wherein the infection score is based at least inpart on the estimated turbidity.

Embodiment A16. The method of claim A15, wherein predicting theinfection state comprises predicting infection in response to theinfection score exceeding a predetermined threshold during each of oneor more successive measurement time periods.

Embodiment A17. The method of claim A15, wherein predicting theinfection state comprises predicting infection in response to theinfection score increasing from a patient baseline over time.

Embodiment A18. The method of claim A15, wherein predicting theinfection state comprises predicting infection based on a rate of changeof the infection score over time.

Embodiment A19. The method of claim A15, wherein predicting theinfection state comprises predicting infection in response to any one ormore of the following: the infection score exceeding a predeterminedthreshold during each of one or more successive measurement timeperiods, the infection score increasing from a patient baseline overtime, and the infection score having an increasing rate of change overtime.

Embodiment A20. The method of claim A1, wherein predicting the infectionstate comprises predicting a probability of infection.

Embodiment A21. The method of claim A1, wherein the fluid conduit iscoupled to a peritoneal dialysis device fluid path.

Embodiment A22. The method of claim A1, wherein the fluid conduit iscoupled to a peritoneal dialysis device tubing set.

Embodiment A23. The method of claim A1, wherein the fluid conduit iscoupled to an inlet of the peritoneal dialysis device tubing set.

Embodiment A24. The method of claim A1, wherein the fluid conduit iscoupled to an outlet of the peritoneal dialysis device tubing set.

Embodiment A25. The method of claim A1, wherein the fluid conduit iscoupled to a drain line of a peritoneal dialysis cycler tubing set.

Embodiment A26. The method of claim A1, wherein the fluid conduit iscoupled to a drain line extension configured to couple to a peritonealdialysis cycler tubing set drain line.

Embodiment A27. The method of claim A1, wherein the fluid conduit iscoupled to a patient line of a peritoneal dialysis cycler tubing set.

Embodiment A28. The method of claim A1, further comprising estimating afluid flow rate in the fluid conduit based at least in part on themeasured optical characteristic, wherein illuminating the patient fluidcomprises activating illumination based on the estimated fluid flowrate.

Embodiment A29. The method of claim A28, further comprising determininga fluid flow state comprising detecting at least one of an ON state andan OFF state based on the estimated fluid flow rate, whereinilluminating the patient fluid comprises activating illumination inresponse to detecting the ON state and ceasing illumination in responseto detecting the OFF state.

Embodiment A30. The method of claim A28, further comprising identifyinga false positive fluid flow state based on the estimated fluid flowrate.

Embodiment A31. The method of claim A29, wherein identifying the falsepositive fluid flow state comprises detecting a predetermined number ofpulses during less than each of two or more successive measurement timeperiods.

Embodiment A32. The method of claim A29, wherein detecting the ON statecomprises detecting a predetermined number of pulses during each of twoor more successive measurement time periods.

Embodiment A33. The method of claim A32, wherein the two or moresuccessive measurement time periods are separated by a predetermineddelay time period.

Embodiment A34. The method of claim A29, wherein estimating the fluidflow rate is based at least in part on applying one or more of a lowpass filter and a high pass filter to the measured opticalcharacteristic.

Embodiment A35. The method of claim A1, further comprising initiatingilluminating the patient fluid and measuring the optical characteristicbased on a user input.

Embodiment A36. The method of claim A1, further comprising detecting abubble in the fluid conduit based at least in part on the opticalmeasurement.

Embodiment A37. The method of claim A1, further comprising providing anindication of the predicted infection state to a user.

Embodiment A38. The method of claim A1, further comprising predicting aparticle concentration of the patient fluid based at least in part onthe measured optical characteristic.

Embodiment A39. The method of claim A1, further comprising predictingbleeding of the patient based at least in part on the measured opticalcharacteristic.

Embodiment A40. The method of claim A1, further comprising predicting animmune response of the patient based at least in part on the measuredoptical characteristic.

Embodiment A41. The method of claim A1, further comprising predictinginfection onset for ascites drainage patients based at least in part onthe measured optical characteristic.

Embodiment A42. The method of claim A1, further comprising predicting afibrin content of the patient fluid based at least in part on themeasured optical characteristic.

Embodiment B 1. A vessel for use in a fluid conduit, comprising:

-   -   an inlet portion;    -   an outlet portion; and    -   an optically transparent measurement portion between the inlet        portion and the outlet portion, wherein the measurement portion        comprises at least two substantially planar surfaces, a        rotational alignment feature, and a depth alignment feature.

Embodiment B2. The vessel of claim B1, wherein the measurement portioncomprises an internal volume configured to receive fluid, wherein theinternal volume comprises radiused corners.

Embodiment B3. The vessel of claim B1, wherein the at least twosubstantially planar surfaces comprise a first planar surface generallyorthogonal to a second planar surface.

Embodiment B4. The vessel of claim B1, wherein the at least twosubstantially planar surfaces comprise a first planar surface oppositeto a second planar surface.

Embodiment B5. The vessel of claim B4, wherein the measurement portioncomprises a generally square cross-section.

Embodiment B6. The vessel of claim B1, wherein at least a portion of themeasurement portion is tapered.

Embodiment B7. The vessel of claim B1, wherein the measurement portioncomprises one or more of copolyester, acrylonitrile butadiene styrene,polycarbonate, acrylic, cyclic olefin copolymer, cyclic olefin polymer,polyester, polystyrene, ultem, polyethylene glycol-coated silicone,zwitterionic coated polyurethane, polyethylene oxide-coated polyvinylchloride, and polyamphiphilic silicone.

Embodiment B8. The vessel of claim B1, further comprising an opaqueconnector coupleable to the inlet portion or the outlet portion.

Embodiment B9. The vessel of claim B8, wherein at least one of the inletportion and the outlet portion is coupleable to the fluid conduit.

Embodiment B10. The vessel of claim B9, further comprising one or moreof a vent cap, clamp, and connector coupled to the fluid conduit.

Embodiment B11. The vessel of claim B9, wherein the vessel is coupled toa peritoneal dialysis drain set extension tubing.

Embodiment B12. The vessel of claim B9, wherein the vessel is coupled toa peritoneal dialysis cycler tubing cassette.

Embodiment B13. The vessel of claim B9, wherein the vessel is coupled toan inlet of a peritoneal dialysis cycler tubing cassette.

Embodiment B14. The vessel of claim B9, wherein the vessel is coupled toa peritoneal dialysis drain bag connector.

Embodiment B15. The vessel of claim B9, wherein the vessel is coupled toa proximal end of a peritoneal dialysis drain bag connector.

Embodiment B16. The vessel of claim B9, wherein the vessel is coupled toa urinary catheter or Foley catheter drain bag.

Embodiment B17. The vessel of claim B9, wherein the vessel is coupled toa central venous drain line.

Embodiment B18. The vessel of claim B9, wherein the vessel is coupled toa hemodialysis blood circulation tube set.

Embodiment B19. The vessel of claim B9, wherein the vessel is coupled toan in-dwelling catheter.

Embodiment B20. The vessel of claim B9, wherein the vessel is coupled toa proximal end of the in-dwelling catheter

Embodiment C1. A patient monitoring device, comprising:

-   -   a housing comprising:    -   a holder configured to releasably receive a portion of a fluid        conduit;    -   at least one illumination source configured to illuminate the        received portion of the fluid conduit; and    -   at least one optical sensor configured to generate a signal,    -   wherein the holder comprise one or more engagement features        configured to orient the received portion of the fluid conduit        in a predetermined rotational and vertical orientation relative        to the at least one illumination source and the at least one        optical sensor.

Embodiment C2. The device of claim C1, wherein the housing comprises alight seal.

Embodiment C3. The device of claim C1, wherein the one or moreengagement features is configured to orient the received portion of thefluid conduit by mating with an alignment feature of the receivedportion of the fluid conduit.

Embodiment C4. The device of claim C1, wherein the one or moreengagement features comprises an open slot.

Embodiment C5. The device of claim C1, wherein the at least oneillumination source comprises a plurality of illumination sources.

Embodiment C6. The device of claim C5, wherein the illumination sourcesare configured to illuminate in a first illumination direction and asecond illumination direction orthogonal to the first illuminationdirection.

Embodiment C7. The device of claim C5, wherein at least two of theillumination sources are configured to illuminate along a first plane ata first wavelength.

Embodiment C8. The device of claim C5, wherein at least another two ofthe illumination sources are configured to illuminate along a secondplane substantially parallel to the first plane.

Embodiment C9. The device of claim C5, wherein the illumination sourcesare configured to illuminate in a first illumination direction and asecond illumination direction opposite the first direction.

Embodiment C10. The device of claim C1, wherein the illumination sourcesare configured to illuminate in a first illumination direction and asecond illumination direction 180 degrees offset from the firstdirection.

Embodiment C11. The device of claim C1, wherein the illumination sourcescomprise a first illumination source configured to emit light at a firstwavelength between about 800 nm and about 900 nm.

Embodiment C12. The device of claim C1, wherein the illumination sourcescomprise a second illumination source configured to emit light at asecond wavelength between about 400 nm and about 450 nm.

Embodiment C13. The device of claim C1, wherein the illumination sourcescomprise a third illumination source configured to emit light at a thirdwavelength between about 500 nm and about 550 nm.

Embodiment C14. The device of claim C1, wherein the illumination sourcescomprise a fourth illumination source configured to emit light at athird wavelength between about 230 nm and about 290 nm.

Embodiment C15. The device of claim C1, wherein the at least one opticalsensor comprises a plurality of optical sensors.

Embodiment C16. The device of claim C1, wherein one or more of the atleast one illumination source and the at least one optical sensorcomprises an anti-reflective coating.

Embodiment C17. The device of claim C1, wherein the holder defines alongitudinal axis, and wherein the at least one optical sensor comprisesa plurality of optical sensors spaced apart parallel to the longitudinalaxis.

Embodiment C18. The device of claim C1, further comprising a controllerconfigured to generate patient data based at least in part on thesignal.

Embodiment C19. The device of claim C1, wherein the patient datacomprises an infection state.

Embodiment C20. The device of claim C1, further comprising a display.

Embodiment C21. The device of claim C1, further comprising a base,wherein the housing is offset and spaced apart from the base.

Embodiment C22. The device of claim C1, wherein the housing comprises aperitoneal dialysis cycler.

Embodiment C23. The device of claim C1, wherein the housing comprises ahemodialysis device.

Embodiment C24. The device of claim C1, wherein the housing isconfigured to couple to one or more of a patient platform and medicalcart.

Embodiment C25. The device of claim C1, wherein the housing comprises aperitoneal dialysis device fluid path.

Embodiment C26. The device of claim C1, wherein the fluid conduit iscoupled to a peritoneal dialysis tubing set.

Embodiment C27. The device of claim C1, wherein the fluid conduit iscoupled to a peritoneal dialysis cycler tubing set.

Embodiment C28. The device of claim C1, wherein the fluid conduit iscoupled to a peritoneal dialysis drain bag connector.

Embodiment C29. The device of claim C1, wherein the fluid conduitcomprises:

-   -   an inlet portion;    -   an outlet portion; and    -   an optically transparent measurement portion between the inlet        portion and the outlet portion, wherein the measurement portion        comprises at least two substantially planar surfaces, a        rotational alignment feature, and a depth alignment feature.

Embodiment C30. The device of claim C29, wherein at least one of therotational alignment feature and the depth alignment feature isconfigured to mate with the one or more engagement features of theholder.

Embodiment C31. The device of claim C1, further comprising a controllerconfigured to generate patient data based at least in part on thesignal.

Embodiment C32. The device of claim C1, wherein the controller islocated remote from the housing, and wherein the device furthercomprises a communication device configured to transmit datarepresentative of the signal to the controller.

Embodiment C33. The device of claim C32, wherein the controller isconfigured to predict an infection score of a patient based at least inpart on the signal.

Embodiment C34. The device of claim C32, wherein the controller isconfigured to predict an infection state of a patient in response to anyone or more of the following: the infection score exceeding apredetermined threshold during each of one or more successivemeasurement time periods, the infection score increasing from a patientbaseline over time, and the infection score having an increasing rate ofchange over time.

Embodiment C35. The device of claim C34, wherein the infection statecomprises a probability of infection.

Embodiment C36. The device of claim C32, wherein the fluid conduit isconfigured to receive a patient fluid and the controller is configuredto estimate turbidity of the patient fluid based at least in part on thesignal, wherein the infection score is based at least in part on theestimated turbidity.

Embodiment C37. The device of claim C32, wherein the controller isconfigured to monitor a trend in infection score predicting infectionresolution of the patient.

Embodiment C38. The device of claim C32, wherein the controller isconfigured to monitor a trend in infection score predicting infectionresolution of the patient by predicting infection resolution in responseto any one or more of the following: the infection score falling below apredetermined threshold during each of one or more successivemeasurement time periods, the infection score decreasing from a patientbaseline over time, and the infection score having a decreasing rate ofchange over time.

Embodiment D1. A method for remote monitoring of a patient, comprising:

-   -   at one or more processors:    -   receiving an optical characteristic measurement of a patient        fluid associated with the patient over a remote communication        link;    -   determining an infection score predicting infection of the        patient, wherein the infection score is based at least in part        on the received optical characteristic measurement; and    -   associating the patient as one of a plurality of patient        infection states based at least in part on the determined        infection score.

Embodiment D2. The method of claim D1, further comprising notifying auser of the associated patient infection state.

Embodiment D3. The method of claim D1, further comprising prompting auser to perform one or more predetermined patient treatment actionsbased on the associated patient infection state.

Embodiment D4. The method of claim D3, wherein the one or morepredetermined patient treatment actions comprises administering a broadspectrum antimicrobial to the patient.

Embodiment D5. The method of claim D3, wherein the one or morepredetermined patient treatment actions comprises administering apathogen-specific antimicrobial to the patient.

Embodiment D6. The method of claim D3, wherein the one or morepredetermined patient treatment actions comprises remotely monitoring atrend in infection score predicting infection resolution of the patient.

Embodiment D7. The method of claim D3, wherein remotely monitoring thetrend in infection score predicting infection resolution comprisespredicting infection resolution in response to the infection scoredecreasing from a patient baseline over time.

Embodiment D8. The method of claim D7, wherein remotely monitoring thetrend in infection score predicting infection resolution comprisespredicting infection resolution based on a rate of change of theinfection score over time.

Embodiment D9. The method of claim D7, wherein remotely monitoring thetrend in infection score predicting infection resolution comprisespredicting infection resolution in response to any one or more of thefollowing: the infection score falling below a predetermined thresholdduring each of one or more successive measurement time periods, theinfection score decreasing from a patient baseline over time, and theinfection score having a decreasing rate of change over time.

Embodiment D10. The method of claim D1, wherein the plurality of patientinfection states comprises a first patient infection state correspondingto a healthy patient.

Embodiment D11. The method of claim D1, wherein the plurality of patientinfection states comprises a second patient infection statecorresponding to a patient brought to a medical care provider.

Embodiment D12. The method of claim D1, wherein the plurality of patientinfection states comprises a third patient infection state correspondingto a patient who has received a broad spectrum antibiotic treatment.

Embodiment D13. The method of claim D1, wherein the plurality of patientinfection states comprises a third patient infection state correspondingto a patient who has received a pathogen-specific antimicrobialtreatment.

Embodiment D14. The method of claim D1, wherein the plurality of patientinfection states comprises a fourth patient infection statecorresponding to a patient who has been hospitalized.

Embodiment D15. The method of claim D1, wherein the plurality of patientinfection states comprises a fifth patient infection state correspondingto a patient who has been transitioned to hemodialysis.

Embodiment D16. The method of claim D1, wherein the predicted infectionis peritonitis.

The foregoing description, for purposes of explanation, used specificnomenclature to provide a thorough understanding of the invention.However, it will be apparent to one skilled in the art that specificdetails are not required in order to practice the invention. Thus, theforegoing descriptions of specific variations of the invention arepresented for purposes of illustration and description. They are notintended to be exhaustive or to limit the invention to the precise formsdisclosed; obviously, many modifications and variations are possible inview of the above teachings. The variations were chosen and described inorder to best explain the principles of the invention and its practicalapplications, and they thereby enable others skilled in the art to bestutilize the invention and various implementations with variousmodifications as are suited to the particular use contemplated. It isintended that the following claims and their equivalents define thescope of the invention.

1.-30. (canceled)
 31. A method of monitoring patient fluid from apatient, comprising: illuminating the patient fluid in a fluid conduitfrom a plurality of illumination directions; measuring an opticalcharacteristic of the illuminated patient fluid using one or moresensors; estimating a fluid flow rate in the fluid conduit based atleast in part on the measured optical characteristic; and predicting aninfection state of the patient based at least in part on the estimatedfluid flow rate and the measured optical characteristic.
 32. The methodof claim 31, wherein illuminating the patient fluid comprises activatingillumination based on the estimated fluid flow rate.
 33. The method ofclaim 31, further comprising determining a fluid flow state comprisingdetecting at least one of an ON state and an OFF state based on theestimated fluid flow rate, wherein illuminating the patient fluidcomprises activating illumination in response to detecting the ON stateand ceasing illumination in response to detecting the OFF state.
 34. Themethod of claim 33, wherein a drain pumping state of a peritonealdialysis cycler corresponds to the ON state and the OFF state.
 35. Themethod of claim 31, further comprising identifying a false positivedrain pumping state based on the estimated fluid flow rate.
 36. Themethod of claim 35, wherein identifying the false positive drain pumpingstate includes not identifying an ON state over two or more successivetime measurement periods.
 37. The method of claim 36, wherein apredetermined delay time period is between the successive timemeasurement periods.
 38. The method of claim 35, wherein the estimatedfluid flow rate comprises a predetermined number of measured pump pulsesover a predetermined duration of fluid flow.
 39. The method of claim 31,wherein the estimated fluid flow rate is further based at least in parton one or more attenuation light intensity measurements from the one ormore sensors.
 40. The method of claim 31, wherein measuring the opticalcharacteristic comprises sampling the patient fluid at about 75 Hz. 41.The method of claim 31, further comprising analyzing a frequencyresponse of the measured optical characteristic, wherein estimating thefluid flow rate is based at least in part on the frequency response. 42.The method of claim 40, further comprising: analyzing a frequencyresponse of the measured optical characteristic; and determining a fluidflow state comprising detecting at least one of an ON state and an OFFstate based on the frequency response.
 43. The method of claim 31,wherein the frequency response between about 0.05 Hz and about 0.2 Hzcorresponds to the ON state, and the frequency response not betweenabout 0.05 Hz and about 0.2 Hz corresponds to the OFF state.
 44. Themethod of claim 41, wherein analyzing the frequency response comprisespassing the measured optical characteristic through one or more filtersto generate a filtered signal.
 45. The method of claim 44, furthercomprising determining a drain pumping state comprising detecting atleast one of an ON state and an OFF state based on the generatedfiltered signal.
 46. The method of claim 45, wherein the filtered signalcomprising a predetermined number of pulses above a predeterminedthreshold corresponds to the ON state.
 47. The method of claim 44,wherein the one or more filters comprises one or more of a first filtercomprising a low pass filter, and a second filter comprising a high passfilter.
 48. The method of claim 31, wherein estimating the fluid flowrate in the fluid conduit based at least in part on one or morenon-optical sensors.
 49. The method of claim 48, wherein the one or morenon-optical sensors comprise one or more of an accelerometer, a pressuresensor, and a microphone.
 50. The method of claim 31, further comprisingdetecting bubbles in the fluid conduit based at least in part on theoptical measurement.
 51. The method of claim 50, further comprisingexcluding the optical measurement corresponding to the detected bubblesfrom the infection state prediction.
 52. The method of claim 31, whereinpredicting the infection state comprises generating an infection score.53. The method of claim 52, wherein the infection score is based atleast in part on the measured optical characteristics of the illuminatedpatient fluid at one or more wavelengths.
 54. The method of claim 52,wherein predicting the infection state comprises predicting infection inresponse to the infection score exceeding one or more predeterminedthresholds during each of one or more successive measurement timeperiods.
 55. The method of claim 52, wherein predicting the infectionstate comprises predicting infection based on a rate of change of theinfection score over time.
 56. The method of claim 52, whereinpredicting the infection state comprises predicting infection inresponse to any one or more of the following: the infection scoreexceeding one or more predetermined thresholds during each of one ormore successive measurement time periods, the infection score changingfrom a patient baseline over time, and the infection score having anincreasing rate of change over time.
 57. The method of claim 52, furthercomprising monitoring a trend in infection score and predictinginfection resolution of the patient based on the monitored trend. 58.The method of claim 57, wherein predicting infection resolutioncomprises predicting infection resolution in response to any one or moreof the following: the infection score falling below one or morepredetermined thresholds during each of one or more successivemeasurement time periods, the infection score decreasing from a patientbaseline over time, and the infection score having a decreasing rate ofchange over time.
 59. The method of claim 31, further comprisingestimating a particle concentration of the patient fluid based at leastin part on the measured optical characteristic.
 60. The method of claim31, wherein the fluid conduit comprises a circular cross-section portionwith a first cross-sectional area and a square cross-section portionwith a second cross-sectional area, wherein the optical characteristicis measured as the fluid transitions from the circular cross-sectionportion to the square cross-section portion.